Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Laboratory rats that have been produced from a genetically manipulated rat EGG or rat EMBRYO, MAMMALIAN. They contain genes from another species.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
The major group of transplantation antigens in the mouse.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
An encapsulated lymphatic organ through which venous blood filters.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
ONCOGENE PROTEINS from papillomavirus that deregulate the CELL CYCLE of infected cells and lead to NEOPLASTIC CELL TRANSFORMATION. Papillomavirus E7 proteins have been shown to interact with various regulators of the cell cycle including RETINOBLASTOMA PROTEIN and certain cyclin-dependent kinase inhibitors.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Glycoproteins found on the membrane or surface of cells.
Established cell cultures that have the potential to propagate indefinitely.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Antibodies produced by a single clone of cells.
Plants or plant parts which are harmful to man or other animals.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.
Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed)
Change brought about to an organisms genetic composition by unidirectional transfer (TRANSFECTION; TRANSDUCTION, GENETIC; CONJUGATION, GENETIC, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome.
Recombinases that insert exogenous DNA into the host genome. Examples include proteins encoded by the POL GENE of RETROVIRIDAE and also by temperate BACTERIOPHAGES, the best known being BACTERIOPHAGE LAMBDA.
Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
The genetic unit consisting of three structural genes, an operator and a regulatory gene. The regulatory gene controls the synthesis of the three structural genes: BETA-GALACTOSIDASE and beta-galactoside permease (involved with the metabolism of lactose), and beta-thiogalactoside acetyltransferase.
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
Annual cereal grass of the family POACEAE and its edible starchy grain, rice, which is the staple food of roughly one-half of the world's population.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.
The functional hereditary units of PLANTS.
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
A group of enzymes that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause GANGLIOSIDOSIS, GM1.
The encapsulated embryos of flowering plants. They are used as is or for animal feed because of the high content of concentrated nutrients like starches, proteins, and fats. Rapeseed, cottonseed, and sunflower seed are also produced for the oils (fats) they yield.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
Diseases of plants.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
A synthetic tetracycline derivative with similar antimicrobial activity.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
A plant species of the genus SOLANUM, family SOLANACEAE. The starchy roots are used as food. SOLANINE is found in green parts.
MAMMARY GLANDS in the non-human MAMMALS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
A type I keratin that is found associated with the KERATIN-5 in the internal stratified EPITHELIUM. Mutations in the gene for keratin-14 are associated with EPIDERMOLYSIS BULLOSA SIMPLEX.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.
Elements of limited time intervals, contributing to particular results or situations.
Proteins prepared by recombinant DNA technology.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990)
A genus of gram negative, aerobic, rod-shaped bacteria found in soil, plants, and marine mud.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Nucleic acid sequences involved in regulating the expression of genes.
The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.
Organisms whose GENOME has been changed by a GENETIC ENGINEERING technique.
The type species of BETARETROVIRUS commonly latent in mice. It causes mammary adenocarcinoma in a genetically susceptible strain of mice when the appropriate hormonal influences operate.
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.
A plant species of the family SOLANACEAE, native of South America, widely cultivated for their edible, fleshy, usually red fruit.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Refers to animals in the period of time just after birth.
Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).
A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.
A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.
A genus of PLANT VIRUSES, in the family CAULIMOVIRIDAE, that are transmitted by APHIDS in a semipersistent manner. Aphid-borne transmission of some caulimoviruses requires certain virus-coded proteins termed transmission factors.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Deoxyribonucleic acid that makes up the genetic material of plants.
An individual that contains cell populations derived from different zygotes.
Prolonged dry periods in natural climate cycle. They are slow-onset phenomena caused by rainfall deficit combined with other predisposing factors.
A circumscribed benign epithelial tumor projecting from the surrounding surface; more precisely, a benign epithelial neoplasm consisting of villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells. (Stedman, 25th ed)
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Vaccines or candidate vaccines derived from edible plants. Transgenic plants (PLANTS, TRANSGENIC) are used as recombinant protein production systems and the edible plant tissue functions as an oral vaccine.
The measurement of an organ in volume, mass, or heaviness.
A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.
Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
Transport proteins that carry specific substances in the blood or across cell membranes.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
Ribonucleic acid in plants having regulatory and catalytic roles as well as involvement in protein synthesis.
A plant genus of the family MALVACEAE. It is the source of COTTON FIBER; COTTONSEED OIL, which is used for cooking, and GOSSYPOL. The economically important cotton crop is a major user of agricultural PESTICIDES.
Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)
A species of gram-negative, aerobic bacteria isolated from soil and the stems, leafs, and roots of plants. Some biotypes are pathogenic and cause the formation of PLANT TUMORS in a wide variety of higher plants. The species is a major research tool in biotechnology.
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Chromosomes in which fragments of exogenous DNA ranging in length up to several hundred kilobase pairs have been cloned into yeast through ligation to vector sequences. These artificial chromosomes are used extensively in molecular biology for the construction of comprehensive genomic libraries of higher organisms.
An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
An individual in which both alleles at a given locus are identical.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.
The ability of organisms to sense and adapt to high concentrations of salt in their growth environment.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
The hollow, muscular organ that maintains the circulation of the blood.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
The observable response an animal makes to any situation.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).

Deletion of a region that is a candidate for the difference between the deletion forms of hereditary persistence of fetal hemoglobin and deltabeta-thalassemia affects beta- but not gamma-globin gene expression. (1/44874)

The analysis of a number of cases of beta-globin thalassemia and hereditary persistence of fetal hemoglobin (HPFH) due to large deletions in the beta-globin locus has led to the identification of several DNA elements that have been implicated in the switch from human fetal gamma- to adult beta-globin gene expression. We have tested this hypothesis for an element that covers the minimal distance between the thalassemia and HPFH deletions and is thought to be responsible for the difference between a deletion HPFH and deltabeta-thalassemia, located 5' of the delta-globin gene. This element has been deleted from a yeast artificial chromosome (YAC) containing the complete human beta-globin locus. Analysis of this modified YAC in transgenic mice shows that early embryonic expression is unaffected, but in the fetal liver it is subject to position effects. In addition, the efficiency of transcription of the beta-globin gene is decreased, but the developmental silencing of the gamma-globin genes is unaffected by the deletion. These results show that the deleted element is involved in the activation of the beta-globin gene perhaps through the loss of a structural function required for gene activation by long-range interactions.  (+info)

Requirement for transcription factor NFAT in interleukin-2 expression. (2/44874)

The nuclear factor of activated T cells (NFAT) transcription factor is implicated in expression of the cytokine interleukin-2 (IL-2). Binding sites for NFAT are located in the IL-2 promoter. Furthermore, pharmacological studies demonstrate that the drug cyclosporin A inhibits both NFAT activation and IL-2 expression. However, targeted disruption of the NFAT1 and NFAT2 genes in mice does not cause decreased IL-2 secretion. The role of NFAT in IL-2 gene expression is therefore unclear. Here we report the construction of a dominant-negative NFAT mutant (dnNFAT) that selectively inhibits NFAT-mediated gene expression. The inhibitory effect of dnNFAT is mediated by suppression of activation-induced nuclear translocation of NFAT. Expression of dnNFAT in cultured T cells caused inhibition of IL-2 promoter activity and decreased expression of IL-2 protein. Similarly, expression of dnNFAT in transgenic mice also caused decreased IL-2 gene expression. These data demonstrate that NFAT is a critical component of the signaling pathway that regulates IL-2 expression.  (+info)

p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis. (3/44874)

p38 mitogen-activated protein kinase (p38) has been extensively studied as a stress-responsive kinase, but its role in development remains unknown. The fruit fly, Drosophila melanogaster, has two p38 genes, D-p38a and D-p38b. To elucidate the developmental function of the Drosophila p38's, we used various genetic and pharmacological manipulations to interfere with their functions: expression of a dominant-negative form of D-p38b, expression of antisense D-p38b RNA, reduction of the D-p38 gene dosage, and treatment with the p38 inhibitor SB203580. Expression of a dominant-negative D-p38b in the wing imaginal disc caused a decapentaplegic (dpp)-like phenotype and enhanced the phenotype of a dpp mutant. Dpp is a secretory ligand belonging to the transforming growth factor beta superfamily which triggers various morphogenetic processes through interaction with the receptor Thick veins (Tkv). Inhibition of D-p38b function also caused the suppression of the wing phenotype induced by constitutively active Tkv (TkvCA). Mosaic analysis revealed that D-p38b regulates the Tkv-dependent transcription of the optomotor-blind (omb) gene in non-Dpp-producing cells, indicating that the site of D-p38b action is downstream of Tkv. Furthermore, forced expression of TkvCA induced an increase in the phosphorylated active form(s) of D-p38(s). These results demonstrate that p38, in addition to its role as a transducer of emergency stress signaling, may function to modulate Dpp signaling.  (+info)

Ganglioneuromas and renal anomalies are induced by activated RET(MEN2B) in transgenic mice. (4/44874)

Multiple endocrine neoplasia type 2B (MEN2B) is an autosomal dominant syndrome characterized by the development of medullary thyroid carcinoma, pheochromocytomas, musculoskeletal anomalies and mucosal ganglioneuromas. MEN2B is caused by a specific mutation (Met918-->Thr) in the RET receptor tyrosine kinase. Different mutations of RET lead to other conditions including MEN2A, familial medullary thyroid carcinoma and intestinal aganglionosis (Hirschsprung disease). Transgenic mice were created using the dopamine beta-hydroxylase promoter to direct expression of RET(MEN2B) in the developing sympathetic and enteric nervous systems and the adrenal medulla. DbetaH-RET(MEN2B) transgenic mice developed benign neuroglial tumors, histologically identical to human ganglioneuromas, in their sympathetic nervous systems and adrenal glands. The enteric nervous system was not affected. The neoplasms in DbetaH-RET(MEN2B) mice were similar to benign neuroglial tumors induced in transgenic mice by activated Ras expression under control of the same promoter. Levels of phosphorylated MAP kinase were not increased in the RET(MEN2B)-induced neurolglial proliferations, suggesting that alternative pathways may play a role in the pathogenesis of these lesions. Transgenic mice with the highest levels of DbetaH-RET(MEN2B) expression, unexpectedly developed renal malformations analogous to those reported with loss of function mutations in the Ret gene.  (+info)

The five amino acid-deleted isoform of hepatocyte growth factor promotes carcinogenesis in transgenic mice. (5/44874)

Hepatocyte growth factor (HGF) is a polypeptide with mitogenic, motogenic, and morphogenic effects on different cell types including hepatocytes. HGF is expressed as two biologically active isotypes resulting from alternative RNA splicing. The roles of each HGF isoform in development, liver regeneration and tumorigenesis have not yet been well characterized. We report the generation and analysis of transgenic mice overexpressing the five amino acid-deleted variant of HGF (dHGF) in the liver by virtue of an albumin expression vector. These ALB-dHGF transgenic mice develop normally, have an enhanced rate of liver regeneration after partial hepatectomy, and exhibit a threefold higher incidence of hepatocellular carcinoma (HCC) beyond 17 months of age. Moreover, overexpression of dHGF dramatically accelerates diethyl-nitrosamine induced HCC tumorigenesis. These tumors arise faster, are significantly larger, more numerous and more invasive than those appearing in non-transgenic littermates. Approximately 90% of female dHGF-transgenic mice had multiple macroscopic HCCs 40 weeks after injection of DEN; whereas the non-transgenic counterparts had only microscopic nodules. Liver tumors and cultured tumor cell lines from dHGF transgenics showed high levels of HGF and c-Met mRNA and protein. Together, these results reveal that in vivo dHGF plays an active role in liver regeneration and HCC tumorigenesis.  (+info)

A concise promoter region of the heart fatty acid-binding protein gene dictates tissue-appropriate expression. (6/44874)

The heart fatty acid-binding protein (HFABP) is a member of a family of binding proteins with distinct tissue distributions and diverse roles in fatty acid metabolism, trafficking, and signaling. Other members of this family have been shown to possess concise promoter regions that direct appropriate tissue-specific expression. The basis for the specific expression of the HFABP has not been previously evaluated, and the mechanisms governing expression of metabolic genes in the heart are not completely understood. We used transient and permanent transfections in ventricular myocytes, skeletal myocytes, and nonmyocytic cells to map regulatory elements in the HFABP promoter, and audited results in transgenic mice. Appropriate tissue-specific expression in cell culture and in transgenic mice was dictated by 1.2 kb of the 5'-flanking sequence of FABP3, the HFABP gene. Comparison of orthologous murine and human genomic sequences demonstrated multiple regions of near-identity within this promoter region, including a CArG-like element close to the TATA box. Binding and transactivation studies demonstrated that this element can function as an atypical myocyte enhancer-binding factor 2 site. Interactions with adjacent sites are likely to be necessary for fully appropriate, tissue-specific, developmental and metabolic regulation.  (+info)

Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very-low-density-lipoprotein receptor. (7/44874)

We have shown previously that human apolipoprotein (apo)C1 transgenic mice exhibit hyperlipidaemia, due primarily to an impaired clearance of very-low-density lipoprotein (VLDL) particles from the circulation. In the absence of at least the low-density-lipoprotein receptor (LDLR), it was shown that APOC1 overexpression in transgenic mice inhibited the hepatic uptake of VLDL via the LDLR-related protein. In the present study, we have now examined the effect of apoC1 on the binding of lipoproteins to both the VLDL receptor (VLDLR) and the LDLR. The binding specificity of the VLDLR and LDLR for apoC1-enriched lipoprotein particles was examined in vivo through adenovirus-mediated gene transfer of the VLDLR and the LDLR [giving rise to adenovirus-containing (Ad)-VLDLR and Ad-LDLR respectively] in APOC1 transgenic mice, LDLR-deficient (LDLR-/-) mice and wild-type mice. Remarkably, Ad-VLDLR treatment did not reduce hyperlipidaemia in transgenic mice overexpressing human APOC1, irrespective of both the level of transgenic expression and the presence of the LDLR, whereas Ad-VLDLR treatment did reverse hyperlipidaemia in LDLR-/- and wild-type mice. On the other hand, Ad-LDLR treatment strongly decreased plasma lipid levels in these APOC1 transgenic mice. These results suggest that apoC1 inhibits the clearance of lipoprotein particles via the VLDLR, but not via the LDLR. This hypothesis is corroborated by in vitro binding studies. Chinese hamster ovary (CHO) cells expressing the VLDLR (CHO-VLDLR) or LDLR (CHO-LDLR) bound less APOC1 transgenic VLDL than wild-type VLDL. Intriguingly, however, enrichment with apoE enhanced dose-dependently the binding of wild-type VLDL to CHO-VLDLR cells (up to 5-fold), whereas apoE did not enhance the binding of APOC1 transgenic VLDL to these cells. In contrast, for binding to CHO-LDLR cells, both wild-type and APOC1 transgenic VLDL were stimulated upon enrichment with apoE. From these studies, we conclude that apoC1 specifically inhibits the apoE-mediated binding of triacylglycerol-rich lipoprotein particles to the VLDLR, whereas apoC1-enriched lipoproteins can still bind to the LDLR. The variability in specificity of these lipoprotein receptors for apoC1-containing lipoprotein particles provides further evidence for a regulatory role of apoC1 in the delivery of lipoprotein constituents to different tissues on which these receptors are located.  (+info)

Overexpression of spermidine/spermine N1-acetyltransferase under the control of mouse metallothionein I promoter in transgenic mice: evidence for a striking post-transcriptional regulation of transgene expression by a polyamine analogue. (8/44874)

We recently generated a transgenic mouse line overexpressing spermidine/spermine N1-acetyltransferase (SSAT) gene under its own promoter. The tissue polyamine pools of these animals were profoundly affected and the mice were hairless from early age. We have now generated another transgenic-mouse line overexpressing the SSAT gene under the control of a heavy-metal-inducible mouse metallothionein I (MT) promoter. Even in the absence of heavy metals, changes in the tissue polyamine pools indicated that a marked activation of polyamine catabolism had occurred in the transgenic animals. As with the SSAT transgenic mice generated previously, the mice of the new line (MT-SSAT) suffered permanent hair loss, but this occurred considerably later than in the previous SSAT transgenic animals. Liver was the most affected tissue in the MT-SSAT transgenic animals, revealed by putrescine overaccumulation, significant decrease in spermidine concentration and >90% reduction in the spermine pool. Even though hepatic SSAT mRNA accumulated to massive levels in non-induced transgenic animals, SSAT activity was only moderately elevated. Administration of ZnSO4 further elevated the level of hepatic SSAT message and induced enzyme activity, but not more than 2- to 3-fold. Treatment of the transgenic animals with the polyamine analogue N1,N11-diethylnorspermine (DENSPM) resulted in an immense induction, more than 40000-fold, of enzyme activity in the liver of transgenic animals, and minor changes in the SSAT mRNA level. Liver spermidine and spermine pools were virtually depleted within 1-2 days in response to the treatment with the analogue. The treatment also resulted in a marked mortality (up to 60%) among the transgenic animals which showed ultrastructural changes in the liver, most notably mitochondrial swelling, one of the earliest signs of cell injury. These results indicated that, even without its own promoter, SSAT is powerfully induced by the polyamine analogue through a mechanism that appears to involve a direct translational and/or heterogenous nuclear RNA processing control. It is likewise significant that overexpression of SSAT renders the animals extremely sensitive to polyamine analogues.  (+info)

Inducible Transgenic Mouse Models , SpringerLink Inducible transgenic mouse models allow for the activation of and the lac and GAL4 inducible systems. The tetracycline-regulated transgenic models are typically Inducible Gene Expression and Gene Modification in Transgenic two major systems have been successfully used in transgenic mice, i.e., the tetracycline-inducible transgenic mice that express that inducible Cre Introduction to Tet expression systems - The how to take viagra 100mg Jackson Laboratory Learn the basics about how Tet-On and Tet-Off inducible systems Introduction viagra high blood pressure to Tet expression systems. in transgenic mice by a tetracycline Conditional and inducible transgene expression in mice Here we describe a triple transgenic mouse system, which combines the tissue specificity of any Cre-transgenic line with the inducibility of the reverse tetracycline Inducible podocyte-specific gene expression in transgenic Inducible podocyte-specific gene expression in ...
Abstract: : Purpose: To establish a binary inducible transgenic mouse model that can be used to elucidate the roles of growth factors, e.g., FGF-7, on corneal biology. It has been suggested that FGF-7 (KGF, keratinocyte growth factor) serves as a paracrine that modulates the growth of corneal epithelial cell. The present studies are to investigate the effect of excess FGF-7 on corneal epithelial cells in a binary tetracycline inducible transgenic mouse line. Methods: A keratocyte-specific 3.2 kb murine keratocan promotor (Kerapr) has been used to prepare Kerapr-rtTA transgenic (KeraprrtTA/+) mice that constitutively overexpress rtTA (reverse tetracycline transcription activator) in cornea. The KeraprrtTA/+ mice were crossed with tet-OFGF7/FGF7 mice to produce compound heterozygous transgenic (KeraprrtTA/+•tet-OFGF7/+) mice, which were fed doxycycline water (0.5 mg/ml) for one week. The experimental mice were i.p. injected with BrdU (100 µg/g body weight) 2 h prior to sacrifice. The enucleated ...
Despite wide academic and commercial interest in the actions of GLP-1, attempts to identify the cellular targets of GLP-1 are hampered by the lack of specificity of antibodies to GLP1R. Our development of a new transgenic mouse model expressing Cre recombinase driven by the glp1r promoter provides an antibody-independent method for the identification and characterization of live cells expressing glp1r, using floxed fluorescent reporter strains. The results illuminate not only which tissues exhibited glp1r fluorescence but also those that did not.. Establishing definitively that the GLP1R protein is produced by all glp1r-fluorescent cells will be important, because our use of Cre recombinase results in a permanent activation of the fluorescent reporters, even in cells that no longer express the receptor as well as in the progeny of cells that have once expressed glp1r. Where neurones were identified, we were able to confirm expression of GLP1R protein by demonstrating functional responsiveness to ...
Purpose: : To develop a mouse line in which a gene of interest can be removed in keratocytes-specific manner upon induction by doxycycline. Methods: : Two transgenes including Kera3.2-int-rtTA and tet-O-Cre were co-microinjected into the fertilized mouse eggs to create transgenic mice. The Kera3.2-int-rtTA /tet-O-Cre transgenic mice were crossed with reporter Rosa26-LacZ mice to obtain Kera3.2-int-rtTA /tet-O-Cre/Rosa26-LacZ triple transgenic mice. The Cre activity was assessed by the detection of whole mount X-gal staining in corneal stroma of triple transgenic mice after administration of doxycycline via drinking water and chow. Results: : We obtained two independent transgenic founder lines in which the Kera3.2-int-rtTA and tet-O-Cre transgenes were co-segregated at the chromosome level. Administration of doxycycline (Dox) to transgenic Kera3.2-int-rtTA /tet-O-Cre mice did not induce expression of LacZ. The Kera3.2-int-rtTA /tet-O-Cre/Rosa26-LacZ triple transgenic mice showed a little bit ...
TY - JOUR. T1 - Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver. AU - Kitteringham, Neil R.. AU - Abdullah, Azman. AU - Walsh, Joanne. AU - Randle, Laura. AU - Jenkins, Rosalind E.. AU - Sison, Rowena. AU - Goldring, Christopher E.P.. AU - Powell, Helen. AU - Sanderson, Christopher. AU - Williams, Samantha. AU - Higgins, Larry. AU - Yamamoto, Masayuki. AU - Hayes, John. AU - Park, B. Kevin. PY - 2010/6/16. Y1 - 2010/6/16. N2 - The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2-/-) are highly susceptible to xenobiotic-mediated toxicity, but the precise molecular basis of enhanced toxicity is unknown. Oligonucleotide array studies suggest that a wide range of gene products is altered constitutively, however no equivalent proteomics analyses have been conducted. To define the range of ...
Am J Pathol. 2012 Feb;180(2):727-37. doi: 10.1016/j.ajpath.2011.10.035. Epub 2011 Dec 7. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Govt
TY - JOUR. T1 - Overexpression of transforming growth factor α in transgenic mice alters nonreproductive, sex-related behavioral differences. T2 - Interaction with gonadal hormones. AU - Hilakivi-Clarke, L.. PY - 1994. Y1 - 1994. N2 - Sexually dimorphic differences in voluntary sodium intake, locomotor activity, immobility in the swim test, and aggressive behavior were found to be altered in transgenic CD-1 mice that overexpressed transforming growth factor α (TGFα). In contrast to nontransgenic CD-1 mice, immobility in the swim test was longer and sodium intake higher in the male TGFα mice than in the female TGFα mice. These findings indicate that the male TGFα mice exhibited feminization of some behaviors. Furthermore, the male TGFα mice were highly aggressive. Castration reversed the behavioral effects in the adult male transgenic mice, but ovariectomy did not reverse the behavioral effects in the adult female transgenic mice. Thus the feminizing effect of TGFα on some nonreproductive ...
Targeting the expression of genes has emerged as a potentially viable therapeutic approach to human disease. In Alzheimers disease, therapies that silence the expression of tau could be a viable strategy to slow disease progression. We produced a novel strain of transgenic mice that could be used to assess the efficacy of gene knockdown therapies for human tau, in live mice. We designed a tetracycline-regulated transgene construct in which the cDNA for human tau was fused to ubiquitin and to luciferase to create a single fusion polyprotein, termed TUL. When expressed in brain, the TUL polyprotein was cleaved by ubiquitin-processing enzymes to release the luciferase as an independent protein, separating the half-life of luciferase from the long-lived tau protein. Treatment of bigenic tTA/TUL mice with doxycycline produced rapid declines in luciferase levels visualized by in vivo imaging and ex vivo enzyme measurement. This new mouse model can be used as a discovery tool in optimizing gene targeting
The Transgenic Mouse / ES Cell Shared Resource assists investigators in generating, maintaining and storing germline-altered mice. This resource, which has been in existence for over 23 years, has generated over 2700 transgenic founder mice from over 750 different DNA constructs and 5000 chimeric mice from over 800 different mouse ES cell clones. Prior to the discovery of the CRISPR/Cas system, the TMESCSR generated over 160 different gene-targeted mice. Since 2013, the TMESCSR has generated over 400 mutant pups by CRISPR/Cas injections from over 100 different projects. The Vanderbilt Transgenic Mouse/ES Cell Shared Resource (TMESCSR) provides services, consultation and collaborations to enable the generation, storage and regeneration of genetically altered mice at Vanderbilt. We have many years of experience in generating novel transgenic mouse models and are happy to discuss your project with you. The following procedures are currently provided on a fee-for-service basis: CRISPR/Cas9 Mouse
The Vanderbilt Genome Editing Resource (VGER) assists investigators in generating, maintaining and storing germline-altered mice in an efficient and cost-effective manner. The VGER provides services, consultation, and collaborations to enable the generation, storage and regeneration of genetically altered mice at Vanderbilt. This resource, which was previously called the Transgenic Mouse ESC Shared Resource (please see announcement letter), has been in existence for over 25 years and has generated 160 unique gene-targeted mice between 1993-2015 and more than 80 genome edited mice using CRISPR-Cas9 since 2014. We have many years of experience in generating novel transgenic mouse models and are happy to discuss your project with you. We provide the following services on a fee-for-service basis: CRISPR-Cas9 Mouse Editing Pronuclear Microinjection of DNAs Embryo Cryopreservation Sperm Cryopreservation In vitro Fertilization and Rederivation Genome-Editing Design and Analysis Services We are sorry, but we
Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior.s profile, publications, research topics, and co-authors
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The biologic relevance of AICD to APP physiology or AD pathology has been proposed, but in vivo evidence that supports the hypothesis has been lacking. The current study was aimed at examining this hypothesis by expressing AICD postnatally and selectively in the forebrain and hippocampal regions of mouse brain. Here, we first show that AICD is present in brain membranes from normal control mice and can be detected by Western blot alone. We further demonstrate that the transgenic mice that were generated in this study express AICD at levels that are similar to those found in APP transgenic mice with FAD mutation, which are two- to threefold higher than in nontransgenic mice. These data strongly support the validity of our mouse model, which was verified further by observing increased expression of KAI1 gene in transgenic mice. Finally, we present evidence that the AICD transgenic mice display robust changes in GSK-3 signaling, which supports an in vivo role for AICD.. The finding that an ...
Missense mutations in APP and PS1 lead to familial forms of AD by different mechanisms. Most PS1 mutations shift γ‐secretase cleavage to increased Aβ42 production, which in turn accelerates cerebral amyloidosis in transgenic mice (Borchelt et al, 1997; Holcomb et al, 1998; Siman et al, 2000). An inverse correlation between the Aβ42 to Aβ40 ratio and the age of onset in familial AD has also been reported (Duering et al, 2005).. Mutations at position Leu 166 in PS1 lead to a severe course of AD pathology, with a very early onset in the third or fourth decade of life. So far, three mutations at position Leu 166 (L166A, L166P and L166H) have been described; the L166P mutation seems to be the most pathogenic (Ezquerra et al, 2000; Moehlmann et al, 2002; Pantieri et al, 2005). Expressing PS1‐L166P in transfected cells resulted in the highest Aβ42 to Aβ40 ratio among several PS1 mutations (Moehlmann et al, 2002). However, in contrast to other PS1 mutations, the L166P mutation has been shown ...
Here we report further our investigation of the role of BRE in HCC. HCC was chemically-induced in the transgenic (TTR-V5-BRE) and non-transgenic littermates, bred with C57BL/6, by intraperitoneal injection of diethylnitosamine (DEN) at 15 days postnatally. At 8 months after injection, the mice were sacrificed, and livers collected for determination of tumor number and maximal size, and for immunohistochemistry. Parts of each liver sample were also dissected visually into tumor and adjacent normal portions for Western Blot analysis of BRE expression. By comparison between the DEN-treated male transgenic mice (n=12) and non-transgenic littermate controls (n=8), we observed significantly increased tumor size shown by the former (p=0.049, Exact Wilcoxon Rank Sum test), with the median tumor size 2-fold larger than the latter. There was, however, no statistically significant difference between tumor numbers of the two groups. Female C57BL/6 mice are known to be less sensitive to DEN-treated ...
Tornavaca O, Pascual G, Barreiro ML, Grande MT, Carretero A, Riera M, Garcia-Arumi E, Bardaji B, González-Núñez M, Montero MA, López-Novoa JM, Meseguer A
Morphologic examinations of mammary neoplasias arising in BALB/c (H-2d) mice carrying the activated rat HER-2/neu oncogene (BALB-NeuT), and in FVB (H-2q) mice bearing the wild-type proto-oncogene (FVB-NeuN), indicate that both conditions result in a very human-like lobular carcinoma of alveolar type …
TY - JOUR. T1 - Immortalization of subpopulations of respiratory epithelial cells from transgenic mice bearing SV40 large T antigen. AU - Ikeda, K.. AU - Clark, J. C.. AU - Bachurski, C. J.. AU - Wikenheiser, K. A.. AU - Cuppoletti, J.. AU - Mohanti, S.. AU - Morris, R. E.. AU - Whitsett, J. A.. PY - 1994. Y1 - 1994. UR - UR - M3 - Article. AN - SCOPUS:0028041963. VL - 267. JO - American Journal of Physiology - Heart and Circulatory Physiology. JF - American Journal of Physiology - Heart and Circulatory Physiology. SN - 0363-6135. IS - 3 part 1. ER - ...
This interesting paper provides clear evidence that amyloid pathology in the double transgenic model causes axonopathy. The results suggest that intracellular Aβ accumulation in double transgenic mice may lead to trafficking defects in axons. While the results are compelling in the double transgenic, no such alterations are observed in single transgenic animals. Furthermore, amyloid pathology in spinal cord and axonopathy appear to be variable features that are not always present in AD patients. As the authors suggest, subtler alterations in signal transduction pathways, leading to misregulation of axonal transport and/or cytoskeletal disruption, may lead to motor deficits not only in AD, but also in other neurodegenerative conditions as well (Ebneth et al., 1998; Morfini et al., 2002; Pigino et al., 2003; Roy et al., 2005). Further studies will be required to determine if intracellular Aβ accumulation leads to motor dysfunction in AD.. ...
TY - JOUR. T1 - Recombinant ret oncogene products induce T lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice. AU - Yan, D.. AU - Isobe, K. I.. AU - Takahashi, M.. AU - Nakashima, I.. PY - 1994/1/1. Y1 - 1994/1/1. N2 - Recombinant ret oncogene products in complete Freunds adjuvant were injected into normal mice and ret oncogene transgenic mice. Spleen cells from the mice immunized with ret proteins were highly proliferated in vitro by the stimulation of ret proteins. The proliferating T cells have CD4+ phenotype and secreated CTLL-2 reactive interleukins. The peritoneal exudate cells from ret proteinimmunized mice suppressed ret-2 lymphoma, which was derived from ret lymphoma transgenic mice. The peritoneal exudate cells from ret melanoma transgenic mice did not suppress ret-2 lymphoma, when they were immunized with ret proteins.. AB - Recombinant ret oncogene products in complete Freunds adjuvant were injected into normal mice and ret oncogene transgenic mice. ...
Ke YD, van Hummel A, Stevens CH, Gladbach A, Ippati S, Bi M, Lee WS, Krüger S, van der Hoven J, Volkerling A, Bongers A, Halliday G, Haass NK, Kiernan M, Delerue F, Ittner LM. Short-term suppression of A315T mutant human TDP-43 expression improves functional deficits in a novel inducible transgenic mouse model of FTLD-TDP and ALS. Acta Neuropathologica 2015 Nov;130(5):661-78 PubMed 26437864 [ ...
Background The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. Methods We performed primary SHIRPA observations during background breeding into the C57BL/6 background and assessed the behaviour of the background-bred animals on the elevated plus maze and in the light-dark test. Our results were analyzed using Chi-square tests and homo- and heteroscedatic T-tests; Results Female transgenic mice displayed increased amounts of head dips and open arm time on the maze, compared to littermate controls. In ...
Transgenic mice with cardiac-restricted overexpression of secretable TNF (MHCsTNF) develop progressive LV wall thinning and dilation accompanied by an increase in cardiomyocyte apoptosis and a progressive loss of cytoprotective Bcl-2. To test whether cardiac-restricted overexpression of Bcl-2 would prevent adverse cardiac remodeling, we crossed MHCsTNF mice with transgenic mice harboring cardiac-restricted overexpression of Bcl-2. Sustained TNF signaling resulted in activation of the intrinsic cell death pathway, leading to increased cytosolic levels of cytochrome c, Smac/Diablo and Omi/HtrA2, and activation of caspases -3 and -9. Cardiac-restricted overexpression of Bcl-2 blunted activation of the intrinsic pathway and prevented LV wall thinning; however, Bcl-2 only partially attenuated cardiomyocyte apoptosis. Subsequent studies showed that c-FLIP was degraded, that caspase-8 was activated, and that Bid was cleaved to t-Bid, suggesting that the extrinsic pathway was activated concurrently in ...
Full Text - CYLD is a deubiquitinating enzyme known for its role as a tumor suppressor whose mutation leads to skin appendages tumors and other cancers. In this manuscript we report that the tumor suppressor CYLD, similarly to other renowned tumor suppressor genes, protects from premature aging and cancer. We have generated transgenic mice expressing the mutant CYLDC/S protein, lacking its deubiquitinase function, under the control of the keratin 5 promoter, the K5-CYLDC/S mice. These mice express the transgene in different organs, including those considered to be more susceptible to aging, such as skin and thymus. Our results show that K5-CYLDC/S mice exhibit epidermal, hair follicle, and sebaceous gland alterations; and, importantly, they show signs of premature aging from an early age. Typically, 3-month-old K5-CYLDC/S mice exhibit a phenotype characterized by alopecia and kyphosis, and, the histological examination reveals that transgenic mice show signs
Nuclear factor κ-light chain enhancer of activated B cells (NF-κB) is a transcription factor that can be activated through canonical or non-canonical signaling pathways, and activation of both pathways has been observed in lung adenocarcinoma tumors. However, the mechanistic links between canonical and non-canonical NF-κB signaling and lung tumorigenesis have not been fully elucidated. Using transgenic mouse models, we demonstrate that canonical NF-κB signaling promotes epidermal growth factor receptor (EGFR)-mediated tumor formation through paracrine signaling to the inflammatory microenvironment, with depletion studies identifying macrophages as a critical cell type promoting EGFR-driven lung tumorigenesis. To study non-canonical NF-κB signaling, we developed a novel transgenic mouse model with inducible over-expression of the non-canonical NF-κB component p52 in the airway epithelium. After injection with the lung carcinogen urethane, p52 over-expression led to increased tumor number, ...
Cystic fibrosis is characterized by dehydration of the airway surface liquid layer with persistent mucus obstruction. |i|Th2|/i| immune responses are often manifested as increased mucous cell density (mucous cell metaplasia) associated with mucus obstruction. IL-33 is a known inducer of |i|Th2|/i| i …
Increased specific activity of Tg-HDL in the presence of human apoA-I and Hpr. (A) Western blot with serial dilutions of plasma from HuapoA-I mice expressing Hpr and apoL-I from a single plasmid (HuapoA-I:Hpr:apoL-I) and normal human plasma. Hpr and apoL-I were detected with monoclonal antibodies. (B) Survival kinetics of naive mice infected with T. b. brucei ILTat 1.25 and then given 300 μl plasma i.v. from HuapoA-I mice expressing Hpr (black diamond; n = 3), apoL-I (black square; n = 3), or both Hpr and apoL-I from a single plasmid (black circle, Hpr:apoL-I; n = 3). The protection obtained by normal human plasma (dilution 1/8) is indicated by the inverted triangle. (C) A280 profile of KBr-purified lipoproteins from human (dashed line) and HuapoA-I mouse plasma expressing Hpr:apoL-I (red line), Hpr (green line), and apoL-I (blue line) separated by size on a Superdex 200 column; fractions 6-7 are void, fractions 8-9 are human LDL, fractions 10-14 are HDLs, and fraction 15 is albumin. (D) ...
The present study showed that levels of BMP6 were increased approximately twofold to fourfold in the hippocampus of patients with AD and in APP tg mice compared to controls; however, no significant differences were detected in the mRNA levels of two other BMPs, BMP2 and BMP7. A striking pattern of BMP6 distribution was also observed in plaque-containing regions of the hippocampus in both AD patients and APP tg mice, where Aβ-containing plaques were surrounded by a ring-like pattern of BMP6 immunoreactivity. Since BMP6 is a secreted protein, and its primary reported role in the brain is in regulating developmental neurogenesis, it is possible that abnormally elevated levels of this protein in AD might affect adult neurogenesis in the hippocampus.. It is important to note that neurogenesis persists in the aged brain; however, its rate declines with increasing age, as revealed by previous studies in rodents (Kuhn et al., 1996; Kempermann et al., 1998), nonhuman primates (Gould et al., 1999), and ...
AP-2 transcription factors play pivotal roles in orchestrating embryonic development by influencing the differentiation, proliferation, and survival of cells. Furthermore, AP-2 transcription factors have been implicated in carcinogenesis, a process where the normal growth and differentiation program of cells is disturbed. To experimentally address the potential involvement of AP-2 in mammary gland tumorigenesis, we generated mice overexpressing AP-2gamma by transgenesis using the mouse mammary tumor virus-long terminal repeat as the transgene-driving promoter unit. In the mammary gland, transgene expression elicited a hyperproliferation that, however, was counterbalanced by the enhanced apoptosis of epithelial cells leading to a hypoplasia of the alveolar epithelium during late pregnancy. In addition, secretory differentiation was impaired, resulting in a lactation failure. In male transgenic mice, the seminal vesicles were sites of strong transgene expression. There the effects of AP-2gamma on ...
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Background: Synucleinopathies of the aging population are a heterogeneous group of neurological disorders that includes Parkinsons disease (PD) and dementia with Lewy bodies (DLB), and are characterized by the progressive accumulation of α-synuclein in neuronal and glial cells.. Toll-like receptor 2 (TLR2), a pattern recognition immune receptor, has been implicated in the pathogenesis of synucleinopathies because TLR2 is elevated in the brains of patients with PD and TLR2 is a mediator of the neurotoxic and pro-inflammatory effects of extracellular α-synuclein aggregates. Therefore, blocking TLR2 might alleviate α-synuclein pathological and functional effects. For this purpose, herein, we targeted TLR2 using a functional inhibitory antibody (anti-TLR2).. Methods: Two different human α-synuclein overexpressing transgenic mice were used in this study. α-synuclein low expresser mouse (α-syn-tg, under the PDGFβ promoter, D line) was stereotaxically injected with TLR2 overexpressing ...
We previously found that adult Kir6.2G132S transgenic female mice (at 8 weeks of age) exhibit hyperglycemia with hypoinsulinemia caused by accelerated apoptosis (26). In the current study, we found that hyperglycemia with hypoinsulinemia in Kir6.2G132S transgenic mice recovers significantly with age. We also show that pancreatic insulin content and the number of β-cells both increase as the Kir6.2G132S transgenic mice become older. The presence of the Kir6.2G132S mutation in the older Kir6.2G132S transgenic mice excludes the possibility that loss of the transgene is responsible for the recovery of β-cell number in the older Kir6.2G132S transgenic mice. In fact, the insulin response to glucose loading was absent in the older Kir6.2G132S transgenic mice. Hence, the recovery of blood glucose and serum insulin are most likely caused by the restoration of pancreatic insulin content resulting from the increased β-cell number in the older Kir6.2G132S transgenic mice. In a preliminary study, we found ...
ACE, as well as all other components of the renin-angiotensin system (RAS), is expressed in a variety of organs, including the kidney (16,19,20). The generation of Ang II by the tissue RAS suggests a role of the peptide as a paracrine modulator of organ function in addition to its function as a circulating hormone. Distinguishing between the importance of systemic and locally produced Ang II is not trivial because pharmacologic inhibitors as well as knockout approaches affect both modes of angiotensin action. Our study used transgenic mice that had been genetically engineered to express a single ACE isoform in a cell type-specific location on the background of an ACE null genotype (10,13). This approach seems well suited to assess the notion of a location-specific role of ACE and to determine the contribution of this restricted expression pattern to the overall health and organ function of an animal.. Previous studies in AT1A and ACE knockout mice as well as earlier experiments with ACE ...
We have used transgenic mouse technology to establish immortalized hepatoma cell lines stably secreting heterologous proteins, such as human α1-antitrypsin and human factor IX. Hepatocyte-specific...
Dr. Yans research focuses on investigating the cellular and molecular mechanisms of cellular stress and survival in neurodegenerative disorders relevant to Alzheimers disease (AD) and Parkinson disease. She has first identified the specific cellular targets (RAGE, receptor for advanced glycation end product; and ABAD, amyloid binding alcohol dehydrogenase) of amyloid-beta peptide (Aβ) and found the evidence of Aβ-mediated neuronal stress. She developed a novel transgenic mouse model relevant to AD and tested the role of RAGE and ABAD in Aβ-mediated cellular perturbation in those AD type mouse models. She was the first to describe the RAGE and ABAD as the functional binding proteins for Aβ. Dr. Yan and her research team are the major group investigating these paradigms. Dr. Yan and her research team have provided evidence that cell surface molecule (RAGE) and mitochondrial enzyme (ABAD) serve as cofactors for promoting and exaggerating neuronal and mitochondrial toxicity in an Aβ-rich ...
In 2007, McCray, Jr. et al from the University of Iowa published a study in which they introduced a vector carrying a human ACE2-coding sequence into wild-type mice and subsequently developed a successful hACE2 transgenic mouse strain. ACE2 expression, which is regulated by the human cytokeratin 18 (K18) promoter in epithelial cells, was observed in the initially infected airway epithelial cells. Studies showed that the K18-hACE2 transgenic mouse infected with a human SARS-CoV strain via intranasal inoculation would not survive. The infection would begin in the airway epithelium, spread to the alveoli and finally out of the lungs to the brain. The infection causes infiltration of macrophages and lymphocytes in the lungs and up-regulation of pro-inflammatory cytokines and chemokines in the lungs and brain. Three to five days following infection, K18-hACE2 mice began to lose weight and become lethargic with labored breathing. All died within seven days. These observations support that transgene ...
Numerous studies using rats and mice have been conducted to examine the cellular mechanisms and processes involved in Alzheimers disease.. A study conducted by Um et al.[105] used transgenic mice Tg-NSE/hPS2m, which expressed the human PS2 mutation and compared them to control mice, who were labeled as non-Tg. Mice were sacrificed from each group and brains were removed and separated so the hippocampus and the extracted mitochondria could be analyzed using western blot analysis.[105] Tunel staining was also used to detect apoptosis.[105] It was found that phosphorylation levels of tau at the Ser404, Ser202, and Thr231 residues in the hippocampus in Tg mice were enhanced.[105] Increased phosphorylation levels of JNK1/2 and p38MAPK along with decreased levels of ERK1/2 phosphorylation were found in transgenic mice (Tg).[105] Tg mice also had higher levels of COX-2 proteins and higher levels of caspase-3 protein levels than control mice.[105] Cytochrome C and Bax protein levels were higher and ...
Tom L. Stephen is the author of this article in the Journal of Visualized Experiments: Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
Nikolaos Svoronos is the author of this article in the Journal of Visualized Experiments: Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
46 A novel transgenic mice has been generated which overexpresses the constitutively activated mutant form of human Rac 1 (Rac-CA), a small GTP-binding protein of the Rho family, in smooth muscle cells. Experiments were conducted to determine whether chronic activation of Rac-1 affects blood pressure (BP) and heart rate (HR). Male Rac-CA and control mice were prepared for chronic cardiovascular monitoring using carotid arterial catheters infused with heparinized saline. BP and HR were measured continuously for more than 4 days. Results show an increased BP in Rac-CA with no change in HR or water intake. BP was consistently higher in Rac-CA mice (Figure), averaging 122±4 vs 109±4 mm Hg during the dark phase (Rac-CA vs Control). HR showed a night/day rhythm with no differences between the Rac-CA and Controls, respectively, 640±15 vs 610±11 bpm (dark) and 572 ±39 vs 578 ±18 (light). These results illustrate that alteration in intracellular signaling (reactive oxygen species) in vascular ...
The risk of heart failure following myocardial infarction is higher in diabetic patients than nondiabetic patients. The mammalian target of rapamycin (mTOR), a key downstream molecule of insulin-phosphoinositide 3-kinase (PI3K)-Akt signaling pathway, plays an important role in cardioprotection. However, the role of cardiac mTOR in ischemic injury in metabolic syndrome has not been well defined. To address this question, we studied the effect of overexpressing cardiac mTOR on cardiac function following ischemia/reperfusion (I/R) in mice with high-fat diet (HFD)-induced obesity. In this study, we used transgenic mice with cardiac-specific overexpression of mTOR (mTOR-Tg) as reported previously. mTOR-Tg and WT mice at 6 weeks old were fed HFD (60% fat by calories) ad libitum for 14 weeks. Control mTOR-Tg and WT mice were fed a normal chow diet (NCD). At 14 weeks after HFD, glucose and insulin tolerance tests demonstrated that HFD generated glucose intolerance and insulin resistance in both mTOR-Tg ...
The signals that determine the size and duration of the primary T cell immune response are not well defined. We studied CD4 T cells at an important checkpoint in their development: when they have become effectors and are ready to rapidly mediate effector functions, both via direct interaction with antigen (Ag)-presenting cells and via cytokine production. We determined the effects of specific Ag and the cytokines interleukin (IL) 2 and transforming growth factor (TGF) beta 1 on T helper cell type 2 (Th2) effector apoptosis versus expansion. Th2-polarized effector cells were generated in vitro from naive CD4 T of T cell receptor transgenic mice, and then restimulated with or without peptide Ag plus Ag-presenting cells and cytokines. In the absence of added cytokines, effector cells cultured without Ag died of apoptosis after 4-7 d. Paradoxically, Ag both induced proliferation and high levels of cytokine synthesis and accelerated effector cell death. IL-2 directly induced proliferation of ...
Absence of lung fibrosis in TGFβ1 overexpressing mice. Figure A shows haematoxylin and eosin staining of Tr+ TGFβ1 transgenic lung tissue. Of note was the abs
In this study, we presented a new line of α-syn A53T conditional transgenic mice to specifically investigate the underlying subcellular and molecular pathogenic pathways leading to α-syn-mediated dysfunction and degeneration of mDA neurons. These A53T mice developed profound movement impairments, especially the rearing activities, perhaps reflecting a severe dysfunction of the nigrostriatal dopaminergic system. Indeed, substantial reduction of dopamine release was observed in the dorsal striatum of 1-month-old A53T mice. Moreover, robust and progressive mDA neurodegeneration was apparent in the 6-month-old mutant mice. Perhaps more interestingly, we identified Nurr1 as an important downstream molecular target of α-syn, in which α-syn promoted a proteasome-dependent degradation of Nurr1 protein, resulting in a preferential dysfunction and loss of mDA neurons. Conversely, a modest suppression of proteasome activities in the mDA neurons ameliorated the α-syn-induced Nurr1 degradation and mDA ...
TY - JOUR. T1 - Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice. AU - Barone, Michele. AU - Scavo, Maria Principia. AU - Maiorano, Eugenio. AU - Di Leo, Alfredo. AU - Francavilla, Antonio. PY - 2014/3. Y1 - 2014/3. N2 - Background: Several studies have demonstrated that cancer can develop with the contribution of bone marrow-derived cancer stem cells. We evaluated the possible involvement of bone marrow-derived stem cells in hepatocarcinogenesis in a hepatitis B virus (HBV) transgenic mouse model. Methods: Bone marrow cells from wild type male mice were transplanted into sublethally irradiated, female, HBV transgenic mice with hepatocarcinoma nodules. Four months later, liver tissue was examined to localize neoplastic nodules/foci and characterize cells by evaluating the Y-chromosome and the hepatocyte lineage marker hepatocyte nuclear factor-1 (HNF1), as well as the HBsAg encoding gene (HBs-Eg) and HBsAg protein (HBs-Pr) (present only in cells of ...
Injury to epidermis and other stratified epithelia triggers profound but transient changes in the pattern of keratin expression. In postmitotic cells located at the wound edge, a strong induction of K6, K16, and K17 synthesis occurs at the expense of the keratins produced under the normal situation. The functional significance of these alterations in keratin expression is not known. Here, we report that overexpression of a wild-type human K16 gene in a tissue-specific fashion in transgenic mice causes aberrant keratinization of the hair follicle outer root sheath and proximal epidermis, and it leads to hyperproliferation and increased thickness of the living layers (acanthosis), as well as cornified layers (hyperkeratosis). The pathogenesis of lesions in transgenic mouse skin begins with a reorganization of keratin filaments in postmitotic keratinocytes, and it progresses in a transgene level-dependent fashion to include disruption of keratinocyte cytoarchitecture and structural alterations in ...
Handling of Mice. The Tg2576 mice were developed by Karen Hsaio (Hsiao et al., 1996) and licensed from the Mayo Foundation for Medical Education and Research (Rochester, MN). Male Tg2576 transgenic mice were bred to normal C57BL6/SJL females at the Bristol-Myers Squibb facility in Wallingford, CT. Mice were housed with a 6:00 AM to 6:00 PM light/dark cycle and allowed free access to food and water. Both male and female mice were used in these studies, and although no differences in Aβ were observed between them, only one sex was used in a single study. Young Tg2576 mice were used between 3 and 6 months of age, whereas aged animals were used at 14 to 17 months. BMS-299897 was synthesized by the Medicinal Chemistry groups of SIBIA Neurosciences, Inc. (now Merck Research Laboratories, San Diego, CA) and Bristol-Myers Squibb. Animals were dosed by oral gavage in a volume of 6 ml/kg in polyethylene glycol, average molecular weight of 400, or a vehicle consisting of 10% propylene glycol, 7.5% ...
106 Gallbladder carcinomas carry poor prognosis and difficulties with treatment, often due to late stage diagnosis, highly malignant nature, and limited knowledge regarding the pathogenesis. Overexpression of erbB2 in gallbladder epithelial cells in BK5.erbB2 transgenic mice leads to development of adenocarcinoma in 90% of the homozygous transgenic mice. This transgenic mouse model provided a useful tool for investigating the mechanism of erbB2 induced development of gallbladder carcinoma. We detected that erbB2 overexpression in transgenic gallbladder epithelial cells was associated with a high level of EGFR and both erbB2 and EGFR were constitutively activated. We further analyzed the downstream of erbB2/EGFR signaling in gallbladder epithelial cells from BK5.erbB2 mice to investigate the mechanism of carcinogenesis. Immunohistochemical analysis revealed that activated Akt was predominantly nuclear in gallbladder epithelial cells from the transgenic mice, but not in nontransgenic mice. Western ...
TY - JOUR. T1 - Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I. AU - Arteaga, Grace M.. AU - Palmiter, Kimberly A.. AU - Leiden, Jeffrey M.. AU - Solaro, R. John. PY - 2000/1/1. Y1 - 2000/1/1. N2 - 1. We compared sarcomere length (SL) dependence of the Ca2+-force relation of detergent-extracted bundles of fibres dissected from the left ventricle of wild-type (WT) and transgenic mouse hearts expressing slow skeletal troponin I (ssTnI-TG). Fibre bundles from the hearts of the ssTnI-TG demonstrated a complete replacement of the cardiac troponin I (cTnI) by ssTnI. 2. Compared to WT controls, ssTnI-TG fibre bundles were more sensitive to Ca2+ at both short SL (1· ± 0·1 μm) and long SL 2·3 ± 0·1 μm). However, compared to WT controls, the increase in Ca2+ sensitivity (change in half-maximally activating free Ca2+; ΔEC50) associated with the increase in SL was significantly blunted in the ssTnI-TG ...
High fat/high cholesterol diets exacerbate β-amyloidosis in mouse models of Alzheimers disease (AD). It has been impossible, however, to study the relationship between atherosclerosis and β-amyloidosis; in those models because such mice were on atherosclerosis-resistant genetic backgrounds. Here we report the establishment of AD model mice, B6Tg2576, that are prone to atherosclerosis. B6Tg2576 mice were produced by back-crossing Tg2576 mice, an AD mouse model overexpressing human amyloid β-protein precursor with the Swedish double mutation, to C57BL/6 mice, a strain susceptible to diet-induced atherosclerosis. An atherogenic diet induced aortic atherosclerosis and exacerbated cerebral β-amyloidosis in B6Tg2576 mice. Compared with age-matched non-transgenic littermates, B6Tg2576 mice developed significantly more diet-induced aortic atherosclerosis. Unexpectedly, normal diet-fed B6Tg2576 mice also developed fatty streak lesions (early atherosclerosis) in the aorta. The aortic atherosclerotic ...
Marxreiter, Franz; Ettle, Benjamin; May, Verena E. L.; Esmer, Hakan; Patrick, Christina; Kragh, Christine Lund; Klucken, Jochen; Winner, Beate; Riess, Olaf; Winkler, Juergen; Masliah, Eliezer; Nuber, Silke ...
TY - JOUR. T1 - HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases. AU - Mangalam, Ashutosh K.. AU - Rajagopalan, Govindarajan. AU - Taneja, Veena D. AU - David, Chella S.. PY - 2008. Y1 - 2008. N2 - Population studies have shown that among all the genetic factors linked with autoimmune disease development, MHC class II genes on chromosome 6 accounts for majority of familial clustering in the common autoimmune diseases. Despite the highly polymorphic nature of HLA class II genes, majority of autoimmune diseases are linked to a limited set of class II-DR or -DQ alleles. Thus a more detailed study of these HLA-DR and -DQ alleles were needed to understand their role in genetic predisposition and pathogenesis of autoimmune diseases. Although in vitro studies using class-II restricted CD4 T cells and purified class II molecules have helped us in understanding some aspects of HLA class-II association with disease, it is difficult to study the role of class II genes in vivo because of ...
A truncated human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA was ligated into an expression vector under the control of the mouse metallothionein-1 gene promotor and upstream of part of the human growth hormone gene to provide splice and polyadenylation signals. Transfection of this construct into human cells resulted in very high levels of ATase expression (more than 300 fmoles/mg protein versus less than 2 fm/mg protein in parent vector transfected control cells). Microinjection of a 4.2 kb fragment of this vector into B6D2F2 mouse embryos and implantation of survivors into pseudopregnant females has so far generated 35 offspring. Southern analysis of tail tip DNA has shown that 11 of the offspring are transgenic for the human ATase gene, between 1 and at least 30 copies of the gene being detected. Human ATase transcripts were detected in total RNA extracted from liver obtained from two male transgenic mice by partial hepatectomy. Cell free extracts of liver samples from five transgenic ...
Introduction: We have previously used a novel transgenic mouse model that expresses an inducible dominant negative mutation of the TGF-β type II receptor (DnTGFβRII) to demonstrate that blocking pro-fibrogenic TGF-β signaling reduces pressure overload-induced interstitial collagen deposition in the heart. The current study utilized DnTGFβRII mice to test the hypothesis that collagen deposition in the pressure overloaded heart is required to maintain structure and prevent cardiac dilation and dysfunction.. Methods: 8 -10 wk old male DnTGFβBRII mice and nontransgenic control (NTG) mice were given 25 mM ZnSO4 in drinking water to induce the expression of DnTGFβRII gene 1 wk prior to transverse aortic constriction (TAC). 120 days after TAC or sham operation, left ventricular (LV) mass, dimension and function were assessed by echocardiography using a high frequency ultrasound probe and interstitial collagen content was assessed in picrosirius red stained sections of LV by light microscopy with ...
We previously described an enhancer variant of Moloney murine leukaemia virus (M-MuLV), ΔMo + SV M-MuLV, in which the enhancers of MuLV have been deleted and replaced with the enhancers of the simian virus 40 (SV40). When this virus is injected into neonatal NIH Swiss mice, pre-B and B-lymphoblastic lymphomas develop with a latency of 17 months. Van Lohuizen et al. (1989) described a line of transgenic mice that carry an activated pim-1 proto-oncogene transgene (Eµ pim-1). They also reported that Eµ pim-1 transgenic mice show greatly accelerated lymphoma development when infected with wild-type M-MuLV at birth. In these experiments, neonatal Eµ pim-1 transgenic mice were infected intraperitoneally with ΔMo + SV M-MuLV. Marked acceleration of T-lymphoid leukaemia was seen. However, 10 of the 11 tumours analysed were found to be negative for the SV40 enhancers, but they still contained M-MuLV DNA as measured by Southern blot analysis. The LTRs on viruses cloned from two such tumours (as well as on
The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX3CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP
en] Using transgenic mice constitutively expressing the human inducible Hsp70, we examined the role of Hsp70 on cell survival after focal cerebral ischemia. Twenty-four hours after permanent occlusion of the middle cerebral artery, no difference in infarct area was detected between Hsp70-transgenic and non-transgenic mice. In the non-transgenic mice, many pyramidal neurons of the ipsilateral hippocampus were observed to be pyknotic. However, in all Hsp70-transgenic mice, hippocampal pyramidal neurons showed normal morphology and no evidence of pyknosis. This suggests that constitutive expression of Hsp70 reduces the extent of damage following permanent middle cerebral artery occlusion ...
Nox2-containing NADPH oxidases are reported to be involved in the development of cardiac fibrosis in response to chronic angiotensin II infusion, but the cellular source(s) of Nox2 involved in fibrosis remains unclear. We investigated the role of endothelial Nox2 in angiotensin II-induced left ventricular hypertrophy (LVH). Male transgenic mice with endothelial-specific overexpression of Nox2 were compared with matched wild-type (wt) littermates after angiotensin II (1.1 mg/kg per day) or saline infusion for 14 days. Basal blood pressure and left ventricular NADPH oxidase activity were similar in wt and transgenic mice. After angiotensin II infusion, both wt and transgenic groups developed similar hypertension (170.2±11.6 vs 170.4±12.3 mm Hg; n=10) and hypertrophy (left ventricular/body weight ratio 4.8±0.2 vs 4.7±0.2 mg/g; and echocardiographic septal thickness increased by 34% wt and 37% transgenic mice; n,10). NADPH oxidase activity was higher in angiotensin II-infused transgenic compared ...
Transgenic mice were produced that carried in their germlines rearranged kappa and/or mu genes with V kappa and VH regions from the myeloma MOPC-167 kappa and H genes, which encode anti-PC antibody. The mu genes contain either a complete gene, including the membrane terminus (mu genes), or genes in which this terminus is deleted and only the secreted terminus remains (mu delta mem genes). The mu gene without membrane terminus is expressed at as high a level as the mu gene with the complete 3 end, suggesting that this terminus is not required for chromatin activation of the mu locus or for stability of the mRNA. The transgenes are expressed only in lymphoid organs. In contrast to our previous studies with MOPC-21 kappa transgenic mice, the mu transgene is transcribed in T lymphocytes as well as B lymphocytes. Thymocytes from mu and kappa mu transgenic mice display elevated levels of M-167 mu RNA and do not show elevated levels of kappa RNA, even though higher than normal levels of M-167 kappa ...
Tissue-specific gene inactivation using the Cre-loxP system has become an important tool to unravel functions of genes when the conventional null mutation is lethal. We report here the generation of a transgenic mouse line expressing Cre recombinase in endothelial cells. In order to avoid the production and screening of multiple transgenic lines we used embryonic stem cell and embryoid body technology to identify recombinant embryonic stem cell clones with high, endothelial-specific Cre activity. One embryonic stem cell clone that showed high Cre activity in endothelial cells was used to generate germline chimeras. The in vivo efficiency and specificity of the transgenic Cre was analysed by intercrossing the tie-1-Cre line with the ROSA26R reporter mice. At initial stages of vascular formation (E8-9), LacZ staining was detected in almost all cells of the forming vasculature. Between E10 and birth, LacZ activity was detected in most endothelial cells within the embryo and of extra-embryonic ...
Background: Degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs early and is ubiquitous in Alzheimers disease (AD). Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive deficits in several transgenic mouse models of AD. Because the LC contains multiple neuromodulators known to affect amyloid β toxicity and cognitive function, the specific role of noradrenaline (NA) in AD is not well understood. Methods: To determine the consequences of selective NA deficiency in an AD mouse model, we crossed dopamine β-hydroxylase (DBH) knockout mice with amyloid precursor protein (APP)/presenilin-1 (PS1) mice overexpressing mutant APP and PS1. Dopamine β-hydroxylase (-/-) mice are unable to synthesize NA but otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal long-term potentiation, and synaptic protein levels were assessed. Results: The modest impairments in spatial memory and hippocampal long-term ...
We hypothesized that AT2R counteracts the growth-promoting effect of Ang II mediated by AT1R via apoptosis in the myocardium. To evaluate the effects of emphasized AT2R stimulation in vivo, we used transgenic mice overexpressing AT2R in a cardiac-specific manner. We evaluated both the sole Ang II effects (subpressor dose of Ang II) and the effects of Ang II and hemodynamic overload mediated by Ang II (pressor dose of Ang II) on cardiomyocyte apoptosis. Furthermore, we used L158809, a specific AT1R antagonist, to eliminate the effects through AT1R. This AT1R antagonist also causes upregulation of endogenous Ang II,27 which selectively stimulates overexpressed AT2R. Therefore, in this experimental system, we could stimulate AT2R selectively and maximally. In none of the conditions, however, did the number of TUNEL-positive nuclei in TG mice differ from that in WT mice, indicating that Ang II infusion for 28 days did not induce apoptosis in the mouse heart. At least, considering that we probably ...
The cAMP-response element-binding protein (CREB) is activated by phosphorylation on serine 133 and mediates the proliferative response to a number of different signals. A mutant CREB with a serine to alanine substitution at position 133 (CREBM1) functions as a dominant-negative inhibitor. Transgenic mice that express the dominant-negative CREB protein in B lymphocytes were developed as a means to study the effects of the inhibition of CREB function on B-cell proliferation and survival. We have shown previously that CREB up-regulates Bcl-2 expression in B cells in response to activation signals. B cells from CREBM1 transgenic mice expressed lower levels of Bcl-2 with and without stimulation. Proliferation of B cells from the transgenic mice was impaired in part by lack of induction of activator protein 1 (AP1) transcription factors. B cells from the transgenic mice were more susceptible to induction of apoptosis with several different agents, consistent with the decreased expression of Bcl-2. ...
The ubiquitin-proteasome system degrades most intracellular proteins, including misfolded proteins. Proteasome functional insufficiency (PFI) was observed in experimental proteinopathies and implicated in many human common diseases but its pathogenic role has not been established because a measure to enhance proteasome function in the cell has not been reported until very recently. We have recently discovered that overexpression of proteasome activator 28α (PA28α) enhances proteasome-mediated removal of abnormal proteins in the cell and protects against oxidative stress in cultured cardiomyocytes (FASEB J 2011; 25(3):883-93). Here we have extended the in vitro discoveries to intact animals. First, we created inducible transgenic mice with cardiomyocyte-restricted PA28α overexpression (CR-PA28αOE). CR-PA28αOE does not alter the homeostasis of normal proteins and cardiac function but increases the degradation of a surrogate misfolded protein in the heart. This marks the establishment of the ...
Using a transgenic mouse model in which the human B-myb cDNA was driven by the basal CMV promoter, this study demonstrates for the first time that B-Myb leads to markedly reduced neointima formation after mechanical injury to the vasculature and to decreased α1(I) collagen mRNA expression in the aorta and femoral artery of adult animals. Three independent transgenic mouse lines were generated, all of which apparently developed and bred normally. An inverse relationship between levels of B-Myb protein and expression of α1(I) collagen mRNA in the adult aorta was demonstrated. A decrease was also seen in α2(V) collagen mRNA levels in the aorta and in cultured aortic SMCs isolated from adult transgenic B-myb mice (data not shown). Importantly, when a femoral artery model of endothelial denudation was used, a dramatic reduction in neointima formation was observed in arteries of transgenic versus WT mice 4 weeks after injury. After injury, the neointimal area and the ratio of the areas of the ...
During a T cell-dependent Ab response, B cells undergo Ab class switching and V region hypermutation, with the latter process potentially rendering previously innocuous B cells autoreactive. Class switching and hypermutation are temporally and anatomically linked with both processes dependent on the enzyme, activation-induced deaminase, and occurring principally, but not exclusively, in germinal centers. To understand tolerance regulation at this stage, we generated a new transgenic mouse model expressing a membrane-tethered gamma2a-reactive superantigen (gamma2a-macroself Ag) and assessed the fate of emerging IgG2a-expressing B cells that have, following class switch, acquired self-reactivity of the Ag receptor to the macroself-Ag. In normal mice, self-reactive IgG2a-switched B cells were deleted, leading to the selective absence of IgG2a memory responses. These findings identify a novel negative selection mechanism for deleting mature B cells that acquire reactivity to self-Ag. This process ...
Alzheimers Imaging Consortium IC-P: Poster Presentations Background: Rosiglitazone, a peroxisome proliferator-activated receptor copy. Because of their high iron content, plaques typically appear as hypo- [gamma] (PPAR[gamma]) agonist, has an anti-inflammatory effect in the intense spots on T2-weighted scans. One of the challenges in imaging brain, decreasing interleukin-1[beta] concentrations in hippocampus and re- plaques is to achieve high-enough resolution and contrast to detect these storing the age-related deficit in long-term potentiation. It also attenuates 50-mm large lesions. While most high-field systems can reach high resolu- learning and memory deficits in a mouse model of Alzheimers disease. Ev- tion, the lack of contrast between the plaques and the parenchyma often idence suggests that activation of microglia and astrocytes contribute to age- impedes their detection. Methods: Transgenic mice over-expressing muta- related neuroinflammatory changes. In this study, relaxometry ...
TY - JOUR. T1 - Dlx5/6-Enhancer Directed Expression of Cre Recombinase in the Pharyngeal Arches and Brain. AU - Ruest, Louis Bruno. AU - Hammer, Robert E. AU - Yanagisawa, Masashi. AU - Clouthier, David E.. PY - 2003/12. Y1 - 2003/12. N2 - Dlx5 and Dlx6, two members of the Distalless gene family, are required for development of numerous tissues during embryogenesis, including facial and limb development. This gene pair is expressed in tandem, transcribed toward each other and separated by a short intergenic region containing multiple putative enhancers. Targeted inactivation of Dlx5 and Dlx6 in mice results in multiple developmental defects in craniofacial and limb structures, suggesting that these genes are crucial for aspects of both neural crest and nonneural crest development. To further investigate potential developmental roles of Dlx5 and Dlx6, we used one of the Dlx5/6 intergenic enhancers to drive Cre recombinase expression in transgenic mice. Crossing Dlx5/6-Cre transgenic mice with ...
The present study assessed the potential functions of interleukin (IL)-32α on inflammatory arthritis and endotoxin shock models using IL-32α transgenic (Tg) mice. The potential signaling pathway for the IL-32-tumor necrosis factor (TNF)α axis was analyzed in vitro. IL-32α Tg mice were generated under control of a ubiquitous promoter. Two disease models were used to examine in vivo effects of overexpressed IL-32α: Toll-like receptor (TLR) ligand-induced arthritis developed using a single injection of lipopolysaccharide (LPS) or zymosan into the knee joints; and endotoxin shock induced with intraperitoneal injection of LPS and D-galactosamine. TNFα antagonist etanercept was administered simultaneously with LPS in some mice. Using RAW264.7 cells, in vitro effects of exogenous IL-32α on TNFα, IL-6 or macrophage inflammatory protein 2 (MIP-2) production were assessed with or without inhibitors for nuclear factor kappa B (NFκB) or mitogen-activated protein kinase (MAPK). Single injection of LPS, but
We have used an aggrecan gene enhancer to generate a transgenic murine line (Acan-CreER-Ires-Luc) expressing firefly luciferase and tamoxifen activatable Cre recombinase (Cre-ER(T2) ). The expression and efficiency of the inducible Cre recombinase activity were tested in double transgenic mice created by crossing the Acan-CreER-Ires-Luc line with a Rosa26-lacZ reporter mouse. The expression pattern of the transgene of our line was restricted to cartilage from embryonic to adult stages. β-galactosidase staining was observed in growth plate, articular cartilage, as well as fibrocartilage of meniscus, trachea, and intervertebral discs. Similar staining was observed in a previously described Agc1 (tm(IRES-creERT2)) murine line. The presence of luciferase in our transgene allows the visualization of the transgene expression in live animals. Weekly measurements from 2 to 8 weeks of age showed a reduction in luminescence in knee joints between 2 and 4 weeks of age, but stabilization thereafter. Following the
Lebanon, NH. Dartmouth researchers identify antiviral, survival job descriptions for T cells. Utilizing a novel transgenic mouse model, Edward Usherwood, PhD of Dartmouths Norris Cotton Cancer Center and collaborators found that CD4 T cells divide into two different populations that each has a different job. One type performs antiviral functions, and the other survives life in the host. The study, Functional Heterogeneity in the CD4+ T Cell Response to Murine Y-Herpesvirus 68, was published in the Journal of Immunology.. The human immune response to viruses and cancer is a complex and multi-pronged effort, but in studies like this one, we are making real progress in understanding how to optimize responses against viruses, explained Usherwood.. Gammaherpesviruses such as the Epstein-Barr virus and the Kaposis Sarcoma-associated herpesvirus can cause cancer, mostly in immune-suppressed populations such as patients with AIDS. While immune control of these viruses is believed to rely on ...
Generation of tTA-TRAF2 transgenic mice. To develop an experimental model to study reverse LV remodeling, we generated a conditional transgenic mouse model (tTA-TRAF2) that overexpresses TRAF2 in the heart, using a cardiac-specific and tetracycline-transactivating factor-regulated promoter (23). The rationale for conditionally overexpressing TRAF2 in the heart was that we have shown previously that sustained expression of TRAF2, a scaffolding protein that coordinates signaling through the type 1 and type 2 TNF receptors, resulted in LV remodeling and LV dysfunction that phenocopies the LV remodeling and LV dysfunction observed with the development of parainflammation in mice with cardiac restricted overexpression of TNF (4). Further, elevated levels of myocardial TRAF2 have been reported to be elevated in HF patients (24). In this conditional tet-off system, the stable tetracycline analog dox (Sigma-Aldrich) inhibits tTA transactivation of the Traf2 transgene in the heart.. Briefly, a murine ...
Background: Protons regulate cellular function by modulating the charge and structure of macromolecules, and proton-extruding and importing transport proteins underlie pH homeostasis. The molecular rotary motor F1Fo complex, ATP synthase, was disclosed at the plasma membrane, but its ligands and functions have not been fully understood. We recently identified a circulating peptide coupling factor 6 (CF6), an endogenous prostacyclin inhibitor, as a novel ligand for F1Fo complex: After binding to protrusive F1, CF6 forces the backward rotation of Fo, resulting in proton import. We investigated the role of interaction between CF6 and ecto-F1Fo complex in the genesis of hypertension and diabetes due to tissue acidosis.. Methods and Results: We generated CF6-overexpressing transgenic mouse (TG) in which CF6 was overexpressed by two times compared with wild type mice (WT). In TG, intracellular pH measured by 31P-magnetic resonance spectroscopy was decreased by 0.1 to 0.15 pH unit in the skeletal ...
Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc complementary DNA and mouse metallothionein 1 promoter-human transforming growth factor α complementary DNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and transforming growth factor α as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction ...
Unlike normal mice, transgenic poliovirus receptor (TgPVR) mice are susceptible to poliovirus injected intravenously or ... In TgPVR1 mice, the transgene encoding the human PVR was incorporated into mouse chromosome 4. These mice express the highest ... PVR transgenic mouse[edit]. Although humans are the only known natural hosts of poliovirus, monkeys can be experimentally ... The newly minted synthetic virus was injected into PVR transgenic mice, to determine if the synthetic version was able to cause ...
University of Utah, Transgenic Mice *^ "2001 Albert Lasker Award for Basic Medical Research". Lasker Foundation. Archived from ... Knockout mice[edit]. Capecchi won the Nobel prize for creating a knockout mouse. This is a mouse, created by genetic ... "The first transgenic mice: An interview with Mario Capecchi". Disease Models and Mechanisms. 1 (4-5): 197-201. doi:10.1242/dmm. ... Knockout mouse Hox genes. Awards. Kyoto Prize (1996). Franklin Medal (1997). Albert Lasker Award for Basic Medical Research ( ...
"Mouse Husbandry, Breeding and Development: Pheromone Effects". Transgenic Mouse Facility, University of California.. ... The Lee-Boot effect is a phenomenon concerning the suppression or prolongation of oestrous cycles of mature female mice (and ... Lee, S. van der; Boot, L.M (1956). "Spontaneous Pseudopregnancy in Mice". Acta Physiol. Pharmacol. Neer. 5 (213).. .mw-parser- ... This effect goes some way to explain why spontaneous pseudopregnancy can occur in mice. The same response is invoked from ...
Greten FR, Wagner M, Weber CK, Zechner U, Adler G, Schmid RM (2002). "TGF alpha transgenic mice. A model of pancreatic cancer ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. "Entrez Gene: TGFA ...
Transgenic mice (e.g. Tg2576) were made which overproduce human APP with the Swedish mutation. As a consequence, the mice can ... The other main effect the discovery of the Swedish mutation had was to provide one transgenic mouse model of Alzheimer's ... The Swedish mutation mice are used to study the effects of amyloid plaques and to develop potential treatments for Alzheimer's ... Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014). "Using mice to model Alzheimer's dementia: an overview ...
Peppel K, Poltorak A, Melhado I, Jirik F, Beutler B (November 1993). "Expression of a TNF inhibitor in transgenic mice". ...
Ren, R. B.; F. Costantini; E. J. Gorgacz; J. J. Lee; V. R. Racaniello (1990-10-19). "Transgenic mice expressing a human ... Hughes, Scott A.; Harshwardhan M. Thaker; Vincent R. Racaniello (2003-12-23). "Transgenic Mouse Model for Echovirus Myocarditis ... Mice producing the human CD155 protein were generated and infected with poliovirus. These mice exhibited all symptoms and ... These mice today are used not only to continue to understand poliovirus pathogenesis but as a means to test the safety of ...
Transgenic mice: * Alzheimer-type Neuropathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein. Nature ... Correlative Memory Deficits, Abeta Elevation, and Amyloid Plaques in Transgenic Mice. Science. 1996;274(5284):99-102. doi: ... Spatial Learning, Exploration, Anxiety, and Motor Coordination in Female APP23 Transgenic Mice with the Swedish Mutation. Brain ... Comparison of Neurodegenerative Pathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein and ...
Koike S, Taya C, Kurata T, Abe S, Ise I, Yonekawa H, Nomoto A (February 1991). "Transgenic mice susceptible to poliovirus". ... He retrieved a sample of mouse brain infected with polio virus and added it to the remaining test tubes, on the off chance that ... Koprowski's attenuated vaccine was prepared by successive passages through the brains of Swiss albino mice. By the seventh ...
Lonberg, Nils; Huszar, Dennis (January 1995). "Human Antibodies from Transgenic Mice". International Reviews of Immunology. 13 ...
"Generating conditional knockout mice". Transgenic Mouse Methods and Protocols. Methods in Molecular Biology. 693. pp. 205-31. ... Schwenk F, Baron U, Rajewsky K (December 1995). "A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene ... Moreover, animals such as mice can be used as models to study human disease. Therefore, Cre-lox system can be used in mice to ... Sakamoto K, Gurumurthy CB, Wagner K (2014), Singh SR, Coppola V (eds.), "Generation of Conditional Knockout Mice", Mouse ...
Several successful approaches have been identified: transgenic mice, phage display and single B cell cloning: As of November ... Lonberg N, Huszar D (1995). "Human antibodies from transgenic mice". International Reviews of Immunology. 13 (1): 65-93. doi: ... who market their TRIANNI Mouse platform. Ablexis, LLC - who market their AlivaMab Mouse platform. Phage display can be used to ... thirteen of the nineteen fully human monoclonal antibody therapeutics on the market were derived from transgenic mice ...
Graham M, Shutter JR, Sarmiento U, Sarosi I, Stark KL (Nov 1997). "Overexpression of Agrt leads to obesity in transgenic mice ... AgRP induces obesity by chronic antagonism of the MC4-R. Overexpression of AgRP in transgenic mice (or intracerebroventricular ... AGRP maps to human chromosome 16q22 and Agrp to mouse chromosome 8D1-D2. Agouti-related protein is expressed primarily in the ... "Mouse PubMed Reference:". Bäckberg M, Madjid N, Ogren SO, Meister B (Jun 2004). "Down-regulated expression of agouti-related ...
Human Monoclonal Antibodies from Transgenic Mice. Chapter 13 in Human Monoclonal Antibodies: Methods and Protocols Ed. Michael ...
al in HY-TCR transgenic mice. Since HY is a male specific antigen, the developing thymocytes would be expected to undergo ... Furthermore, female mice TNCs were found to contain five times more thymocytes than male mice, and less than 4% of them were ... "Thymic nurse cell multicellular complexes in HY-TCR transgenic mice demonstrate their association with MHC restriction." ... found in their study that one-fourth of the nurse cells isolated from mice were double-positives for K5 and K8, while the rest ...
Human Monoclonal Antibodies from Transgenic Mice. Chapter 13 in Human Monoclonal Antibodies: Methods and Protocols Ed. Michael ... Alirocumab was discovered by Regeneron Pharmaceuticals using its "VelocImmune" mouse, in which many of the genes coding for ... it took only about 19 months from when they first immunized mice with PCSK9 until they filed their IND. Alirocumab was co- ...
Transgenic pets[edit]. Mice expressing GFP under UV light (left & right), compared to normal mouse (center) ... "New lines of GFP transgenic rats relevant for regenerative medicine and gene therapy". Transgenic Research. 19 (5): 745-63. doi ... "Fluorescent puppy is world's first transgenic dog".. *^ Voss-Andreae J (2005). "Protein Sculptures: Life's Building Blocks ... It has also been found that new lines of transgenic GFP rats can be relevant for gene therapy as well as regenerative medicine. ...
doi:10.1016/s0361-9230(01)00639-6. Rondi-Reig, L (2001). "Transgenic mice with neuronal overexpression of bcl-2 gene present ... Martinou, JC (1994). "Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and ... Gianfranceschi, L (1999). "Behavioral visual acuity of wild type and bcl2 transgenic mouse". Vision Research Journal. 39: 569- ... Behavior of transgenic mice reveals a role for developmental cell death". Brain Research Bulletin. 57: 85-91. ...
Joyce C, Freeman L, Brewer HB, Santamarina-Fojo S (June 2003). "Study of ABCA1 function in transgenic mice". Arteriosclerosis, ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Luciani MF, Denizot ... Human data from patients and controls were used to demonstrate the translation of mouse findings in human disease. Mutations in ... Knockout mouse models of AMD treated with agonists that increase ABCA1 in loss of function and gain of function experiments ...
Crawley, Jacqueline N. (2007-05-11). What's Wrong With My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice. John ... Crusio, Wim E. (March 2013). "Mouse behavioral testing. How to use mice in behavioral research - by Douglas Wahlsten". Genes, ... He is known for his laboratory research on the behavior of mice, and for his theoretical writings on a wide range of other ... doi:10.1111/j.1601-183X.2012.00864.x. CS1 maint: discouraged parameter (link) Wahlsten, Douglas (2010-10-22). Mouse Behavioral ...
What's wrong with my mouse: Behavioral phenotyping of transgenic and knockout mice, Wiley-Interscience, Hoboken, NJ (2007) 523 ... She has co-edited 4 books and is the author of What's Wrong With my Mouse? Behavioral Phenotyping of Transgenic and Knockout ... Behavioral phenotyping of transgenic and knockout mice". Genes, Brain and Behavior. 1 (2): 131. doi:10.1034/j.1601-183X. ... Behavioral Phenotyping of Transgenic and Knockout Mice". Genes, Brain and Behavior. 7 (7): 831. doi:10.1111/j.1601-183X. ...
Transgenic mice: *. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, ... and amyloid plaques in transgenic mice". Science. 274 (5284): 99-102. doi:10.1126/science.274.5284.99. PMID 8810256.. ... and motor coordination in female APP23 transgenic mice with the Swedish mutation". Brain Research. 956 (1): 36-44. doi:10.1016/ ... in a cellular model and reverses tau pathology in transgenic mouse models of Alzheimer's disease". Alzheimer's & Dementia. 4 (4 ...
Cardiac dysfunction in the HIV-1 transgenic mouse treated with zidovudine. Lab Invest 2000;80:187-97. Lewis W, Simpson JF, ...
"Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice". Proc. Natl. Acad. Sci. U.S.A. 91 (12): 5359 ... Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta ... "Mouse PubMed Reference:".. *^ Wang DD, Bordey A (December 2008). "The astrocyte odyssey". Prog. Neurobiol. 86 (4): 342-67. doi: ... "Mouse Genome Informatics".. *^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, ...
Lalonde R, Eyer J, Wunderle V, Strazielle C (May 2003). "Characterization of NFH-LacZ transgenic mice with the SHIRPA primary ... The protocol has been used to test several mutant mice, including dystrophin-deficient mutants, transgenic models of ... Lalonde R, Dumont M, Staufenbiel M, Strazielle C (February 2005). "Neurobehavioral characterization of APP23 transgenic mice ... This protocol became known as the "modified SHIRPA" and has been used to screen for dominant phenotypes in mice. Sanger Mouse ...
... synaptic and behavioral deficits in aged human tau transgenic mice". Journal of Biological Chemistry. 288 (6): 4056-65. doi: ... "Transgenic Mouse Models of Alzheimer Disease: Developing a Better Model as a Tool for Therapeutic Interventions". Current ... and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model. [Article]". Journal of ... "Silencing of CDK5 Reduces Neurofibrillary Tangles in Transgenic Alzheimer's Mice". Journal of Neuroscience. 30 (42): 13966- ...
2007). "Development of autoimmunity in IL-14alpha-transgenic mice". J. Immunol. 177 (8): 5676-86. doi:10.4049/jimmunol.177.8. ... "Development of autoimmunity in IL-14alpha-transgenic mice". J. Immunol. 177 (8): 5676-86. doi:10.4049/jimmunol.177.8.5676. PMID ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Nogami S, Satoh S, ... 2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci ...
"ADAM 12 protease induces adipogenesis in transgenic mice". Am. J. Pathol. 160 (5): 1895-903. doi:10.1016/S0002-9440(10)61136-4 ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. Gilpin BJ, Loechel ...
"Pronuclear injection for the production of transgenic mice". Nature Protocols. 2 (5): 1206-1215. doi:10.1038/nprot.2007.145. ... Mating plugs are used by many species, including several primates, kangaroos, bees, reptiles, rats, rodents, scorpions, mice, ...
2002). "Doppel-induced cerebellar degeneration in transgenic mice". Proc. Natl. Acad. Sci. U.S.A. 98 (26): 15288-93. doi: ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. "Entrez Gene: PRND ... 1999). "Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel". J. ... 2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci ...
... furin cleavage site not essential for secretion and integration of ZP3 into the extracellular egg coat of transgenic mice". Mol ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.. ... Bleil JD, Wassarman PM (1980). "Mammalian sperm-egg interaction: identification of a glycoprotein in mouse egg zonae pellucidae ... "Human homolog of the mouse sperm receptor". Proc. Natl. Acad. Sci. U.S.A. 87 (16): 6014-8. Bibcode:1990PNAS...87.6014C. doi ...
Transgenic mice generated through exogenous DNA microinjection of an embryo's pronucleus are also considered to be hemizygous ... A transgenic can later be bred to homozygosity and maintained as an inbred line to reduce the need to confirm the genotypes of ...
A genetically modified tomato, or transgenic tomato, is a tomato that has had its genes modified, using genetic engineering. ... Clinical trials have been conducted on mice using tomatoes expressing antibodies or proteins that stimulate antibody production ... Tomatoes have been used as a model in map-based cloning, where transgenic plants must be created to prove that a gene has been ... Zhang, H. X.; Blumwald, E. (2001). "Transgenic salt-tolerant tomato plants accumulate salt in foliage but not in fruit". Nature ...
During the same time period in which Semenza was developing EPO-transgenic mice, Peter Ratcliffe, a physician and kidney ...
Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) in the brain, which suggest ... "Mouse PubMed Reference:".. *^ Schellenberg GD, Bird TD, Wijsman EM, Orr HT, Anderson L, Nemens E, White JA, Bonnycastle L, ... the ability to stabilize beta-catenin complex leads to hyperactive degradation of beta-catenin in the brains of transgenic mice ... in brains of mice expressing mutant presenilin 1". Nature. 383 (6602): 710-3. Bibcode:1996Natur.383..710D. doi:10.1038/383710a0 ...
For this reason, poliovirus couldn't be made in many laboratories until transgenic mice having a CD155 receptor on their cell ...
"The structure of the human CD2 gene and its expression in transgenic mice.". EMBO J. 7 (6): 1675-82. PMC 457152. PMID 2901953. ...
The Spi-B factor was shown to be crucial in initiating viral replication in certain strains of transgenic mice.[10] The protein ...
"Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic beta2-adrenoceptor ... correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice". ... "Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse ...
Doxycycline driven overexpression of TGF β1 in the lungs of transgenic mice result in a time-dependent inflammatory response ... overexpressing transgenic mice exposed to high dose doxycycline. Acute exposure to high concentrations of chlorine gas induces ... Mice that survive this initial onslaught go on to demonstrate an increase in lung collagen content, and decreased lung ... Test articles passing muster in vitro can be evaluated in a number of in vivo models (usually in mice) of ALI including ...
Retroviral mutations can be developed to make transgenic mouse models to study various cancers and their metastatic models. ... Genus Betaretrovirus; type species: Mouse mammary tumour virus. *Genus Gammaretrovirus; type species: Murine leukemia virus; ... Retroviruses that cause tumor growth include Rous sarcoma virus and Mouse mammary tumor virus. Cancer can be triggered by proto ...
Brigid Hogan FRS (1943-): British developmental biologist noted for her contributions to stem cell research and transgenic ... and the technique behind gene targeting and knockout mice.[325] ... of the technique of homologous recombination of transgenic DNA ...
... especially SOD1G93A mice.[23] However, many drug targets that were shown to be effective in the SOD1G93A transgenic mouse ... As of 2018, there are about 20 TARDBP mouse models, a dozen FUS mouse models, and a number of C9orf72, PFN1, and UBQLN2 mouse ... The first animal model for ALS was the SOD1G93A transgenic mouse,[g] which was developed in 1994. It expresses about 20-24 ... These trials in humans went ahead on the basis of positive results in SOD1 transgenic mice, which are not a good animal model ...
... transgenic mouse model of Alzheimer's disease". Neurobiol. Dis. 39 (3): 409-22. PMC 2913404. PMID 20493257. doi:10.1016/j.nbd. ... "Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice". Proc. Natl ... knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time". Neurobiol. Dis. 14 (1 ... "The Diabetes Drug Liraglutide Prevents Degenerative Processes in a Mouse Model of Alzheimer's Disease". The Journal of ...
"In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome ... as mice studies have shown that starvation-induced autophagy was impaired in atg7-deficient mice.[60] ... The study in mice fed with olive oil resulted in an increase in nerve cell autophagy activation compared to controls that had ... A study of mice shows that autophagy is important for the ever-changing demands of their nutritional and energy needs, ...
Capecchi, Mario R. (2001). "Generating mice with targeted mutations". Nature Medicine. 7 (10): 1086-90. doi:10.1038/nm1001-1086 ... "Global Review of the Field Testing and Commercialization of Transgenic Plants: 1986 to 1995" (PDF). The International Service ... "Global Status of Transgenic Crops in 1997" (PDF). ISAAA Briefs No. 5.: 31. ... "Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA" ...
"In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome ... as mice studies have shown that starvation-induced autophagy was impaired in atg7-deficient mice.[68] ... A study of mice shows that autophagy is important for the ever-changing demands of their nutritional and energy needs, ... When the Beclin1 gene was altered to be heterozygous (Beclin 1+/-), the mice were found to be tumor prone.[90] However, when ...
For early-onset Huntington's (ages 5-15), both transgenic mice and mouse striatal cell lines show brain specific histone H3 ... are first tested in mouse models of SMA created through a variety of mutations in the mouse SMN1 gene. If the mice show ... Trichostatin A is also a class I and II HDACi that rescues fear learning in a fear conditioning paradigm in transgenic AD mice ... Tested on: mouse (M), only mouse cells (MC), human (H), Drosophila (D), rat (R). Successful treatment: yes (y), yes but with ...
Weissmann C, Flechsig E (2003). "PrP knock-out and PrP transgenic mice in prion research". Br. Med. Bull. 66: 43-60. doi: ... In mice, this same deletion phenotypically varies between Alzheimer's mouse lines, as hAPPJ20 mice and TgCRND8 mice show a ... A common approach is using PrP-knockout and transgenic mice to investigate deficiencies and differences.[27] Initial attempts ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.. ...
"Transgenic mice with a reduced core body temperature have an increased life span". Science. 314 (5800): 825-8. Bibcode:2006Sci ... The life extension varies for each species, but on average there was a 30-40% increase in life span in both mice and rats.[28] ... Mice, which are warm blooded, have been engineered to have a reduced core body temperature which increased the lifespan ... Faulks, SC; Turner, N; Else, PL; Hulbert, AJ (Aug 2006). "Calorie restriction in mice: effects on body composition, daily ...
GPERKO mice[edit]. GPER knockout mice have also been generated, and exhibit obesity, cardiovascular dysfunction, insulin ... "Lessons in estrogen biology from knockout and transgenic animals". Annu. Rev. Physiol. 67: 285-308. doi:10.1146/annurev. ... βERKO mice[edit]. Females[edit]. *The uterus, vagina, and oviducts are normal.[14] The ovary is normal prior to puberty, and ... of those of normal mice, and further diminish with age, at 13% of those of normal mice by 16 weeks of age.[14] There are ...
"Transgenic plants of Nicotiana tabacum L. express aglycosylated monoclonal antibody with antitumor activity". Biotecnologia ... Mannose has recently been reported in a vertebrate, the mouse, Mus musculus, on the cell-surface laminin receptor alpha ...
The Kandel lab has also performed important experiments using transgenic mice as a system for investigating the molecular basis ... In 2008, he and Daniela Pollak discovered that conditioning mice to associate a specific noise with protection from harm, a ... "Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene". PNAS. 94 (9): 4761-4765. ... "Hippocampal long-term depression and depotentiation are defective in mice carrying a targeted disruption of the gene encoding ...
"Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in ... "Mouse PubMed Reference:".. *^ a b c d e f Steel JC, Waldmann TA, Morris JC (January 2012). "Interleukin-15 biology and its ... In one study with mice blocking IL-15 with an antibody led to the reversal of autoimmune intestinal damage.[24] In another ... It has been demonstrated that two isoforms of IL-15 mRNA are generated by alternatively splicing in mice. The isoform which had ...
a b Transgenic harvest Editorial, Nature 467, pages 633-634, 7 October 2010, doi:10.1038/467633b. Retrieved 9 November 2010 ... Laboratory work with GMOs classified as low risk, which include knockout mice, are carried out in PC1 lab. This is the case for ... Currently available transgenic crops and foods derived from them have been judged safe to eat and the methods used to test ... Transgenic animals have genetically modified DNA. Animals are different from plants in a variety of ways-biology, life cycles, ...
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.. ... Transgenic studiesEdit. Studies in model animal systems that delete or overexpress the Alox5 gene have given seemingly ... In mice, for example, Alox5 overexpression may decrease the damage caused by some types yet increase the damage caused by other ... Alox5 gene knockout mice exhibit an increase in the lung tumor volume and liver metastasis of Lewis lung carcinoma cells that ...
... starting with work in germ-free transgenic mice, in which fecal transplants from people with PD had worse outcomes. Some ... Transgenic rodent models that replicate various aspects of PD have been developed.[132] Using the neurotoxin 6-hydroxydopamine ... "Transgenic rodent models of Parkinson's disease". Acta Neurochirurgica. Supplement. Acta Neurochirurgica Supplementum. 101: 89 ...
... "sea mice" (an example of gikun). In English translations of these haiku, they are usually called "sea slugs». According to the ... study found that a lectin from Cucumaria echinata impaired the development of the malaria parasite when produced by transgenic ...
2000). "Transgenic mice expressing a truncated form of the high mobility group I-C protein develop adiposity and an abnormally ...
"Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington's Disease Mutation". The Journal of ... "The use of the R6 transgenic mouse models of Huntington's disease in attempts to develop novel therapeutic strategies". NeuroRx ... "Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological genotype in transgenic mice ... "First Transgenic Monkey Model Of Huntington's Disease Developed". ScienceDaily. 2008-05-19. Retrieved 2008-08-10.. ...
Because non-human primates are much closer to humans than mice genetically, the successful creation of transgenic marmosets ... At the moment we use mice with mutant genes that are associated with Parkinsons to search for new drugs to treat the condition ... The birth of this transgenic marmoset baby is undoubtedly a milestone, stem cell expert Dr. Gerald Schatten, of the University ... Transgenic marmosets are potentially useful models for research into infectious diseases, immunology and neurological disorders ...
  • In an attempt to determine the susceptibility of haploid, round spermatids to neoplastic transformation by this oncogene, transgenic mice were generated that harbored a chimeric gene composed of the SV40 T-antigen genes fused to the 5' and 3' flanking sequences of the mouse protamine 1 gene. (
  • Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo. (
  • The mouse agouti gene encodes an 131 amino acid paracrine signaling molecule that instructs hair follicle melanocytes to switch from making black to yellow pigment. (
  • We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P (
  • 1 2 To evaluate the phenotype in more detail, this gene has been introduced in mice, the APOE*3-Leiden mouse. (
  • Transgenic mice expressing the human APOE*3-Leiden gene were generated and bred with C57Bl/6J females as described earlier. (
  • Previous work showed no evidence of increased mRNA or transcriptional activation of the GSK3β gene in the mice, despite an increase in kinase activity. (
  • To establish a small animal model of severe acute respiratory syndrome (SARS), we developed a mouse model of human severe acute respiratory syndrome coronavirus (SARS-CoV) infection by introducing the human gene for angiotensin-converting enzyme 2 (hACE2) (the cellular receptor of SARS-CoV), driven by the mouse ACE2 promoter, into the mouse genome. (
  • Here we study the effects of cell death inhibition by using a transgenic mouse in which the powerful antiapoptotic gene bcl-2 is expressed in neurons. (
  • Capecchi, M.R. (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. (
  • An alternative approach to selective ablation of cells in vivo uses transgenic techniques to target expression of a toxic gene product. (
  • Furthermore, gene microarray analysis indicated that the MIKK mice had increased expression of genes encoding proteins implicated in protein ubiquitination and proteasomal degradation, including the muscle-specific ubiquitin ligase MuRF1. (
  • 1. A transgenic mouse, whose genome comprises an indicator gene under the control of a transcriptional regulatory element, wherein said transcriptional regulatory element comprises a MEF2 binding site and said indicator gene is (a) expressed in embryonic cardiac tissue, (b) not expressed in adult cardiac tissue, and (c) expressed in adult cardiac tissue in response to hypertrophic signals. (
  • 6. The transgenic mouse of claim 1 , wherein said indicator gene is selected from the group consisting of lacZ, a gene encoding green fluorescent protein and a gene encoding luciferase. (
  • In a subset of hyperglycemic L1 mice, we observed decreased mRNA expression of AdipoR2 in liver and muscle, as well as decreased peroxisome proliferator-activated receptor (PPAR)α target gene expression in liver, raising the possibility that deterioration of adiponectin/AdipoR2 signaling via PPARα activation contributes to the progression from compensated insulin resistance to diabetes. (
  • In this transgenic mouse, the firefly luciferase gene was introduced into the translation start site of the mouse Bdnf gene using a bacterial artificial chromosome (BAC). (
  • Transgenic founders were then crossed to MHC class II deficient mice: the GenPharm C2d line, now known as the Taconic Transgenic Model B6.129- H2-Ab1 tm1Gru , which has the I-A beta gene inactivated by gene targeting in 129S2-derived ES cells and the unexpressed I-E alpha allele found in the C57BL/6 haplotype. (
  • This volume provides readers with a historical foundation in standard techniques and a comprehensive update on the latest methods used in making gene-modified mice. (
  • In Transgenic Mouse Methods and Protocols, Marten Hofker and Jan van Deursen have assembled a multidisciplinary collection of readily reproducible methods for working with mice, and particularly for generating mouse models that will enable us to better understand gene function. (
  • Such alternative strategies as random mutagenesis and viral gene transduction for studying gene function in the mouse are also presented. (
  • Up-to-date and highly practical, Transgenic Mouse Methods and Protocols demonstrates clearly for both novice and expert investigators how to make novel transgenic mouse models, and how to use them effectively to understand the role of gene function in human health and disease. (
  • We have now analyzed tumorigenesis in mice bearing a Bcl2 transgene controlled by Vav gene regulatory sequences (VavP), which confer expression in multiple hematopoietic lineages. (
  • Young VavP- Bcl2 mice had an overabundance of enlarged germinal centers and greatly elevated numbers of cycling B cells that had undergone IgH class switching and V-gene hypermutation. (
  • 5 The tumorigenic potential of Bcl2 has been explored in transgenic mouse models that mimic the translocation by expressing the gene in B cells under the control of an Igh enhancer (Eμ). (
  • Recently, it was reported that one popular line of these mice--mice possessing a BAC transgene with a D(2) dopamine receptor (Drd2) promoter construct coupled to an enhanced green fluorescent protein (eGFP) reporter--had abnormal striatal gene expression, physiology, and motor behavior. (
  • However, in more commonly used inbred strains of mice (C57BL/6, FVB/N) that were hemizygous for the transgene, the Drd2-eGFP BAC transgene did not alter striatal gene expression, physiology, or motor behavior. (
  • Immunological assessments carried out for the first time on a transgenic protein revealed that post-translational processing subsequent to gene transfer into an alien species introduced new antigenicities that turned a previously harmless protein into a strong immunogen. (
  • As practically all the transgenic proteins involve cross-species gene transfer, they will be subjected to different post-translational processing, and hence they too, will have the potential to become immunogenic. (
  • Abstract To explore the compatibility of skeletal and cardiac programs of gene expression, transgenic mice that express a skeletal muscle myogenic regulator, bmyf5, in the heart were analyzed. (
  • Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF 165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter. (
  • To investigate the antagonistic effect of IL-12 p40 on IL-12 activity in vivo, we generated transgenic (Tg) mice in which p40 gene was regulated by a liver-specific promoter. (
  • Before injection into fertilized mouse eggs, the plasmid was digested with Hin dIII and Xho I, and the resultant 2.8-kb fragment of SAP-IL-12 p40 gene was isolated and used for microinjection. (
  • We examined the possibility that continuous activation of the human brain renin-angiotensin system causes cognitive impairment, using human renin (hRN) and human angiotensinogen (hANG) gene chimeric transgenic (Tg) mice. (
  • I have no experience working with mice models, but why, for example, in pronuclear injection (or even other methods of transgenesis), is the injected gene of interest randomly integrated? (
  • To understand whether autophagy can indeed enhance HBV replication in vivo , we generated HBV transgenic mice with liver-specific knockout of the Atg5 gene, a gene critical for the initiation of autophagy. (
  • The HBV Tg05 mouse line, which contains the 1.3-mer HBV genome and productively replicates HBV in the liver ( 21 ), was crossed with the mouse line that contains the floxed Atg5 gene (Atg5 f/f ). (
  • Therefore, survival rate and chymase activity in the heart and skin were measured in transgenic mice carrying the human chymase gene [ 9 ]. (
  • The experiment was performed in male transgenic mice (18-20 weeks of age) carrying the human chymase gene (Tg) [ 9 ] and male wild-type C57BL/6 mice (WT). (
  • In this case, the mice were created by knocking out the gene that expresses a protein named FKBP12.6 that binds to special receptors in heart cells that control the release of calcium ions into the cells interior. (
  • Researcher with green glowing baby mice that have a jellyfish gene that codes for GFP (green fluorescent protein), seen with a normal mouse. (
  • A virus was used to introduce the gene into fertilised mice eggs. (
  • First evidence for neurotoxic in vivo properties of A β came from a transgenic mouse model expressing murine A β under the control of the mouse Neurofilament-light gene (NF-L) promoter, ensuring neuronal expression. (
  • To study the involvement of PECAM-1 in signaling cascades in vivo, we used the major histocompatibility (MHC) I gene promoter to target ectopic PECAM-1 expression in transgenic mice. (
  • STAT5a, a modulator of milk protein gene expression during lactation, was localized to the nuclei of ductal epithelial cells of 6-week-old virgin PECAM-1 transgenics, but not in control mice. (
  • In vivo, conditional knock-out of ß-catenin gene (Ctnnb1) did not have significant effects on corneal morphogenesis or homeostasis, but abolished OSSN formation in Dox-treated Krt12rtTA/rtTA/tetO-FGF-7/tetO-Cre/Ctnnb1lox(E2-6)/lox(E2-6) mice. (
  • This study engineered an hCAR-BAC-transgenic (hCAR-TG) mouse model by integrating the 8.5-kbp hCAR gene as well as 73-kbp upstream and 91-kbp downstream human genomic DNA into the genome of CAR-null mice. (
  • Another mouse has had a gene altered that is involved in glucose metabolism and runs faster, lives longer, is more sexually active and eats more without getting fatter than the average mouse (see Metabolic supermice). (
  • The CASIS mice include 16 week-old C57Bl female mice, 5 wild type and 5 transgenic MuRF-1 knockout. (
  • Control APOE*3-Leiden (n=6) and C57Bl/6J (n=6) mice received standard mouse chow for 9 months. (
  • In an attempt to provide a mouse model for these diseases, a hybrid MHC class II molecule between the peptide binding domains of human HLA-DRA and HLA-DRB*0401 and the membrane proximal domains of mouse I-E (H2-E) was engineered and co-injected into C57BL/6 fertilized eggs. (
  • C57BL/6J.VavP- Bcl2 13 and C57BL/6J.Eμ- Bcl2 mouse strains 7 were propagated as transgene heterozygotes through matings with healthy C57BL/6J mice. (
  • Transgenic offspring were identified at 4 weeks of age from their elevated peripheral blood leukocyte counts, using a Z2 Coulter counter (Beckman Coulter, Fullerton, CA). GK5 mice, 14 which transgenically express an antimouse CD4 antibody and consequently lack all peripheral CD4 T cells, were on a C57BL/6By.C-H2 bm1 /ByJ background. (
  • In this report, we describe the generation of a TCR transgenic mouse (2D2) specific for the MOG 35-55 peptide on the C57Bl/6 background. (
  • Expression of interleukin 9 was required for optimal tumor growth in vivo, as one of the tumors studied, which had lost the transgene, was much more efficiently transplanted into transgenic than in normal mice. (
  • Fortunately, a transgenic model is now available to fill the unmet need for an in vivo experimental platform for COVID-19 research. (
  • Several parameters indicated that muscle loss in the MIKK mice was due to increased catabolism of muscle proteins: high circulating and excreted amounts of protein breakdown products, high oxygen consumption and heat production, and high protein turnover in ex vivo assays. (
  • Led by Akihiko Takashima of the RIKEN Brain Science Institute in Saitama, Japan, first author Kentaro Tanemura and colleagues report their analysis of tau transgenic mice that enable the study of tau-induced neurodegeneration in vivo. (
  • In this article, we describe a novel approach for producing transgenic animals by transducing spermatogonial stem cells in vivo using a retrovirus vector. (
  • The technique overcomes the drawback of the in vitro-transduction approach, and will be useful as a novel method for producing transgenic animals as well as providing a means for analyzing the self-renewal and differentiation processes of spermatogonial stem cells in vivo. (
  • Therefore, we have studied different aspects of Btc transgenic female's and male's reproduction, including puberty initiation, ovulation, in vivo and in vitro oocyte maturation, sperm parameters, in vivo and in vitro fertilization, and implantation in order to uncover the reason for their reduced fertility. (
  • The expression pattern at the cellular level, studied by immunohistochemistry, revealed a high expression of Btc in the transgenic cumulus cells, which could be an explanation for the altered in vivo and in vitro fertilization. (
  • These mice permit photoinhibition or photostimulation both in vitro and in vivo. (
  • To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. (
  • Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. (
  • These results suggest that p40 functions as an IL-12 antagonist in vivo, and that Th1 responses in p40 Tg mice are significantly reduced. (
  • Thus, these Tg mice could be a useful model to evaluate the inhibitory effect of p40 on IL-12-mediated various immune responses in vivo. (
  • Thus, these mice would be useful to evaluate the function of p40 as an IL-12 antagonist in vivo. (
  • To resolve this discrepancy and to understand whether autophagy indeed affects HBV replication in vivo , we decided to use HBV transgenic mice that we previously established in our laboratory for studies. (
  • METHODS: Tumors from TySV40 transgenic mice were characterized in vivo and in vitro by immunohistology, compound microscopy, and electron microscopy. (
  • Our data suggest that these mouse lines will be useful models for ratiometric monitoring of Cl i in specific cell types in vivo . (
  • To address in vivo impact of this IRS-1 variant on whole body glucose homeostasis and insulin signalling, we have generated transgenic mice overexpressing it (Tg972) and evaluated insulin action in the liver, skeletal muscle and adipose tissue and assessed glucose homeostasis both under a normal diet and a high-fat diet. (
  • In summary, the hCAR-TG mice developed by this study represent a valid model for studying in vivo function and regulation of hCAR and its splicing variants. (
  • However, some mice survive due to chromosomal rearrangement of proliferating hepatocytes resulting in loss of significant functional components of the transgene. (
  • In these mice, the liver parenchyma is replaced by the transgene deficient hepatocytes within about 8 weeks. (
  • In some Alb-uPA mice there is complete loss of the transgene, and these mice eventually develop hepatocellular adenomas and carcinomas. (
  • Unlike most of the work using BAC mice, this interesting study relied upon mice backcrossed on the outbred Swiss Webster (SW) strain that were homozygous for the Drd2-eGFP BAC transgene. (
  • As reported, SW mice were very sensitive to transgene expression. (
  • Thus, the use of inbred strains of mice that are hemizygous for the Drd2 BAC transgene provides a reliable tool for studying basal ganglia function. (
  • The transgene and several skeletal muscle-specific genes were expressed only in patchy areas of the heart in heterozygous mice. (
  • Expression of the transgene was associated with an increase in Ca 2+ -stimulated myofibrillar ATPase in myofibrils obtained from the left ventricles of 42-day-old bmyf5 mice. (
  • Ectopic expression of MyoD in the hearts of transgenic mice activated some muscle-specific skeletal sarcomeric genes and resulted in embryonic lethality with severe cardiac abnormalities in fetuses heterozygous for the transgene. (
  • Furthermore, we have established embryonic stem (ES) cells from the blastocysts of the transgenic mouse that carry the 1.2 kb promoter-LacZ reporter transgene. (
  • Three Tg mouse lines were generated, and they expressed the p40 transgene predominantly in liver. (
  • In the present study, we generated p40 transgenic (Tg) 3 mice predominantly expressing the transgene in liver and found that IL-12-mediated Th1 responses were reduced significantly due to the antagonistic activity of p40 in these p40 Tg mice. (
  • Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. (
  • Preparation of the human chymase transgene and production of Tg mice were described previously in detail [ 9 ]. (
  • to characterize the mice with regard to transgene expression and pathology and to characterize the resulting tumors histologically. (
  • However, the mice did not pass the transgene to their offspring, and the impact and applicability of this experiment were, therefore, limited. (
  • Background -This study documents (1) the progression of atherosclerosis along the entire arterial tree in APOE*3-Leiden mice after 1, 4, 6, 9, and 12 months of a high-fat/high-cholesterol (HFC) diet and (2) the amount and phenotype of DNA-synthesizing and apoptotic cells in different lesion types after 6 months of HFC diet. (
  • The MIKK mice exhibited profound muscle loss, and crossing the MIKK mice to the MISR mice reversed this phenotype. (
  • Crossing the MIKK mice to MuRF -/- mice showed partial rescue of the muscle-wasting phenotype of the MIKK mice. (
  • These mutant mice display a dominant behavioral phenotype that consists of circling, hyperactivity, and head tossing, reminiscent of the shaker/waltzer class of mutants, and they display a recessive homozygous sublethal phenotype. (
  • Mice lacking Btc are viable, fertile and show no overt phenotype, but transgenic mice overexpressing Btc exhibit a whole array of phenotypical alterations. (
  • We discuss the cardiac phenotype in these models and compare Cx expression between mice and men. (
  • To test whether the phenotype of disease is related to the particular TCR expressed by the pathogenic cell, we have generated several lines of TCR transgenic mice using receptors cloned from pathogenic Th1 or Th2 cells. (
  • We have, therefore, investigated the pretumor phenotype of this new mouse model in the hope of gaining insight into the enigmatic early stages of human follicular lymphoma. (
  • Strain-specific regulation of striatal phenotype in Drd2-eGFP BAC transgenic mice. (
  • Overexpression of glutaminyl cyclase, the enzyme responsible for pyroglutamate abeta formation, induces behavioral deficits and glutaminyl cyclase knock-out rescues the behavioral phenotype in 5XFAD mice. (
  • Transgenic mice carrying an albumin promoter linked to mouse urokinase type plasminogen (uPA) activator have functionally compromised hepatocytes. (
  • In this paper, we show that agouti expression driven by the human beta-ACTIN promoter produces obese yellow transgenic mice and that this can be used as an assay for agouti activity. (
  • Transgenic mice expressing human INSR cDNA from the transthyretin ( Ttr ) promoter were intercrossed with Insr +/− mice. (
  • We report the first vascular endothelial cell lineage-specific (including angioblastic precursor cells) 1.2 kb promoter in transgenic mice. (
  • Moreover, deletion analysis of this promoter region in transgenic embryos revealed multiple elements that are required for the maximum endothelial cell lineage-specific expression. (
  • PURPOSE: To characterize intraocular tumors that arise by in situ transformation in the choroid-retinal pigment epithelium (RPE) in transgenic mice bearing the SV40 oncogene under the control of the mouse tyrosinase promoter. (
  • First, we generated transgenic mice expressing Cl-Sensor under the control of the mouse Thy1 mini promoter. (
  • We also describe a transgenic mouse reporter line for Cre-dependent conditional expression of Cl-Sensor, which was targeted to the Rosa26 locus and by incorporating a strong exogenous promoter induced robust expression upon Cre-mediated recombination. (
  • METHODS: Transgenic mice were generated that express T-antigen under the control of the murine interstitial retinol binding protein promoter. (
  • Later, a transgenic mouse model expressing human APP with the Swedish mutation (APP23) under the control of the murine Thy1-promoter was reported, showing significant hippocampal CA1 neuron loss (−14%) at the age of 14 to 18 months. (
  • Scientists make mice strains with multiple mutations in less than a month without using embryonic stem cells. (
  • As a result of this poor viral tissue tropism in mice, commonly used wild-type mouse strains are not optimal for studying infections of the newly discovered coronavirus. (
  • A handful of transgenic mouse strains exist that express various forms of tau, but they either die at a young age or differ markedly from the tau pathology seen in AD. (
  • If different donors were used for the different mouse strains, that can also affect the results because not all donor cells engraft with equal efficiency into immunodeficient mice, depending upon the donor genotype. (
  • The peripheral T-cell compartment was larger in the VavP- Bcl2 mice than in Eμ- Bcl2 strains and, notably, CD4 T cells were 5-fold increased over normal. (
  • I thought it was important to bring up this older post to share with the scientist solutions community some recent advances in fluorescent protein carrying mouse strains. (
  • Asante EA , Linehan J , Desbruslais M , Joiner S , Gowland I , Wood A , BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. (
  • Expression of agouti during the middle part of the hair growth cycle in wild-type mice produces a yellow band on an otherwise black hair. (
  • At days 3 and 7 postinoculation, SARS-CoV replicated more efficiently in the lungs of transgenic mice than in those of wild-type mice. (
  • Therefore, transgenic mice were more susceptible to SARS-CoV than were wild-type mice, and susceptibility was associated with severe pathologic changes that resembled human SARS infection. (
  • In 2007, Dr. Paul McCray, et al from the University of Iowa published a study in which they introduced a vector carrying a human ACE2-coding sequence into wild-type mice and subsequently developed a successful hACE2 transgenic mouse strain. (
  • Neither the MISR nor the MIKK mice exhibited any changes compared with wild-type mice in insulin sensitivity when fed a normal or high-fat diet. (
  • Successive matings of Btc transgenic males and females mice with wild-type mice revealed a decrease in litter size as compared with litters produced by control matings. (
  • Currently, 3 carcinogenicity packages have been initiated, with 2 preliminary 5/28-day studies in rasH2 wild-type mice already completed. (
  • The avoidance rate in wild-type mice gradually increased. (
  • Importantly, these effects of telomerase overexpression cannot be attributed to dramatic differences in telomere length in aged K5-Tert mice compared to wild-type mice, as shown by quantitative telomeric FISH. (
  • There were no differences in pancreatic morphology between Tg972 and wild-type mice, however when insulin secretion was evaluated in isolated islets, it was significantly reduced in Tg972 mice islets at any glucose concentration tested. (
  • Thus, in vitro mutagenesis followed by the generation of transgenic mice should allow us to identify important functional elements of the agouti protein. (
  • Tissue-specific tumorigenesis can be induced in transgenic mice by the directed expression of simian virus 40 (SV40) large tumor (T) antigen. (
  • The ubiquitous unregulated expression of agouti in mice carrying dominant yellow alleles is associated with pleiotropic effects including increased yellow pigment in the coat, obesity, diabetes and increased tumor susceptibility. (
  • Here, we show that in spite of this elevated tumor incidence and the initial lower survival, K5-mTert mice show an extension of the maximum lifespan from 1.5 to 3 months, depending on the transgenic line, which represents up to a 10% increase in the mean lifespan compared to wild-type littermates. (
  • Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. (
  • Tumor cell lines were established and characterized for growth and metastatic potential in the eyes of nude mice. (
  • Radiolabeled transgenic tumor cells preferentially localized in the liver after intravenous injection in normal mice. (
  • Tumor size statistics in 4 groups of transgenic mice! (
  • Hi all, I have 4 different groups of transgenic mice (A-D) and want to compare tumor sizes each other (group by group). (
  • Transgenic mice generated to carry cloned oncogenes and knockout mice lacking tumor suppressing genes have provided good models for human cancer. (
  • Transgenic modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the amyloid precursor protein and the presenilins that cause familial forms of Alzheimer's disease. (
  • To model GSS, we generated transgenic mice expressing cellular prion protein (PrP C ) lacking the glycosylphosphatidyl inositol (GPI) anchor, denoted PrP(ΔGPI). (
  • A transgenic mouse assay for agouti protein activity. (
  • Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte- secreted apoE3 and apoE4 lipoproteins," Journal of Neuroscience , vol. 18, no. 9, pp. 3261-3272, 1998. (
  • Alzheimer-type neuropathology in transgenic mice overexpressing V717F β -amyloid precursor protein," Nature , vol. 373, no. 6514, pp. 523-527, 1995. (
  • In addition, transgenic mice had more severe pulmonary lesions, including interstitial hyperemia and hemorrhage, monocytic and lymphocytic infiltration, protein exudation, and alveolar epithelial cell proliferation and desquamation. (
  • Infectious protein aggregates from the skin of human patients can cause disease in mice. (
  • Boosting levels of a the immunosuppressive protein PD-L1 in blood stem cells halts diabetes in a mouse model of the disease. (
  • The Takashima mice are remarkable, as they appear to express high levels of the mutant tau protein in only a very few cells in the brain: that is, in some of the pyramidal cells of the hippocampus. (
  • Because of the very limited number of cells expressing the mutant protein, it appears that the mice will survive (unlike the Lewis/Hutton mice) to advanced age. (
  • Using transgenic techniques, Blasco's team have managed to eliminate the Trf1 protein from mouse bone marrow, in order to explore its role in the tissue's function. (
  • We believe a transgenic chicken system offers a number of advantages over either plant or other transgenic animal systems for protein production. (
  • RESEARCH DESIGN AND METHODS- To examine adiponectin's contribution to insulin action, we analyzed adiponectin levels and activation of AMP-activated protein kinase (AMPK) in insulin receptor transgenic/knockout mice (L1), a genetic model of resistance to insulin's indirect effects on hepatic glucose production. (
  • We report that L1 mice display hyperadiponectinemia, associated with the inability to lower plasma glucose levels and blunted hepatic AMP-activated protein kinase (AMPK) response to adiponectin. (
  • The present invention relates to the use of thy1-FP (fluorescent protein) non-human transgenic animals such as mice to screen for ophthalmic agents that can be used to treat corneal dry eye syndrome and/or retinal neuropathies associated with glaucoma and/or age-related macular degeneration. (
  • The ACE2 protein has been previously identified as a receptor for SARS-CoV-1, and the expression of the human ACE2 protein in mice renders them susceptible to SARS-CoV-2," explained Dr. Turner, Professor and Vice President for Research at Texas Biomed. (
  • Kuo said, "This suggests that, at least in mice with the human proteins, these gastrointestinal symptoms are an intrinsic defect caused by the mutant protein, rather than being caused by abnormalities in brain function. (
  • A novel transgenic mice has been generated which overexpresses the constitutively activated mutant form of human Rac 1 (Rac-CA), a small GTP-binding protein of the Rho family, in smooth muscle cells. (
  • In this study the transgenic mouse TgCRND8, which encodes a mutant form of the amyloid precursor protein 695 with both the Swedish and Indiana mutations and develops extracellular amyloid beta-peptide deposits as early as 2-3 months, was investigated. (
  • Immune Reactions to Transgenic Protein Serious. (
  • In addition, the transgenic protein promoted immune reactions against multiple other proteins in the diet. (
  • The researchers found that the transgenic protein was processed differently and provoked immune reactions not exhibited by the native protein (see later). (
  • Transgenic aA1 protein was compared with the non-transgenic protein on Western blot, a technique that separates different forms of the protein arising from post-translational processing. (
  • The b-chain in the transgenic protein also showed a number of other bands besides the major and minor forms present in the native protein. (
  • Surprisingly, no differences in the neocortical synaptic bouton number as well as in synaptophysin protein levels were detected during aging or in comparison with age-matched nontransgenic control mice [ 27 ]. (
  • CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase. (
  • Brain atypical proteinase K-resistant prion protein (PrP res ) of porcine PrP transgenic mice infected with cattle bovine spongiform encephalopathy (BSE) (lane 2) or sheep BSE agents (lane 4). (
  • Correcting diastolic dysfunction by Ca 2+ desensitizing troponin in a transgenic mouse model of restrictive cardiomyopathy," Journal of Molecular and Cellular Cardiology , vol. 49, no. 3, pp. 402-411, 2010. (
  • Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome," American Journal of Physiology , vol. 289, no. 3, pp. (
  • Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. (
  • We describe here how transgenic mice designed to model these diseases have substantially contributed to the identification and validation of many promising new therapies, and conversely how they have quickly and cost effectively eliminated several targets with unrealized expectations. (
  • This supports the use of the K18-hACE2 transgenic mouse model for COVID-19 research. (
  • As a pioneer in genetics and mouse model research, JAX has a 90-year history of supporting researchers around the world with precisely-developed mouse models of human disease and powerful preclinical research solutions. (
  • As an integral part of the JAX mission to improve human health and to ensure that researchers worldwide have access to this model, JAX is utilizing its state-of-the-art breeding techniques to grow a new K18-hACE2 transgenic mouse colony rapidly. (
  • This technology now referred to as transgenic mouse technology has revolutionized virtually all fields of biology and provided new genetic approaches to model many human diseases in a whole animal context. (
  • It is unclear what relevance these mice may have for studies of Alzheimer's disease, but it is an interesting model of tau-mediated cell dysfunction in the hippocampus. (
  • In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. (
  • A team at the Spanish National Cancer Research Centre (CNIO) led by Mar-a Blasco has successfully created a transgenic mouse model that simulates the disease in humans. (
  • We have previously reported the development of a transgenic mouse model for prostate cancer derived from PB-Tag transgenic line 8247, henceforth designated the TRAMP (transgenic adenocarcinoma mouse prostate) model. (
  • A transgenic mouse developed at Cincinnati Children's to model the deadly childhood immune disease HLH (hemophagocytic lymphohistiocytosis) may play a key role in saving lives during the COVID-19 virus pandemic. (
  • Further, fingolimod (a sphingoshine 1 phosphate receptor modulator) rescues reduced levels of BDNF in several regions of the brain including the striatum and hippocampus, and ameliorates symptoms in a mouse model of Rett syndrome 11 . (
  • To develop the model, the investigators will create "transgenic" mice with both human tau, and a "bioluminescent" imaging reporter that is regulated by the formation of tau prions. (
  • Publishing their results preliminarily on the open source journal BioRxiv , researchers at Texas Biomed were among a limited group of scientists nationwide given early access to newly developed transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) to test whether these mice can be used as a small animal model to assess SARS-CoV-2 infection. (
  • Researchers at Texas Biomed not only found that the human transgenic mice serve as a good model for SARS-CoV-2 infection but also discovered key indicators of an inflammatory immune response (activation of the immune system). (
  • In addition to establishing the K18 hACE2 transgenic mouse model supplied by The Jackson Laboratory, researchers also found these transgenic mice were the most susceptible to severe COVID-19 disease progression and produced what is known as a chemokine storm. (
  • Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism. (
  • This transgenic mouse model claims to use the genetic mutation that is known to accompany human forms of the disease. (
  • The mouse model may also be able to display early signs of constipation and other gastrointestinal problems that are a common harbinger of the disease in humans. (
  • The UCSF mouse model is said to not only be the first to display the full gastrointestinal symptoms. (
  • A mouse model that closely models the human disease would, therefore, be of significant benefit. (
  • A metabolomic study of the CRND8 transgenic mouse model of Alzheimer's disease. (
  • To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor (VEGF) upregulation. (
  • These chimeric mice have been developed as a mouse model of human hypertension induced by activation of the human RAS. (
  • Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. (
  • We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy. (
  • Abschuetz O, Osen W, Frank K, Kato M, Schadendorf D, Umansky V. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma. (
  • So, we believe that Tg972 mice may represent a useful model to elucidate the interaction between genetic and environmental factors in insulin resistance pathogenesis. (
  • CONCLUSIONS: These mice represent an animal model system for human trilateral retinoblastoma, in which retinoblastomas are accompanied by pineal tumors. (
  • Since their initial generation in the mid 1990s, transgenic mouse models of Alzheimers's disease (AD) have been proven to be valuable model systems which are indispensable for modern AD research. (
  • Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease. (
  • Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema. (
  • Electrophoretic profiles and antibody labeling of PrP res detected with monoclonal antibodies Sha31 (A) or 12B2 (B). Profiles produced by cattle (lane 1) and sheep BSE (lane 3) before passage in the porcine mouse model are shown for comparison. (
  • 2004. Anti-hepatitis B virus activity of ORI-9020, a novel phosphorothioate dinucleotide, in a transgenic mouse model. (
  • A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (Mus musculus) that has had its genome altered through the use of genetic engineering techniques. (
  • Mice are a useful model for genetic manipulation and research, as their tissues and organs are similar to that of a human and they carry virtually all the same genes that operate in humans. (
  • Comprehensive and authoritative, Transgenic Mouse: Methods and Protocols is a valuable resource for both novice and expert researchers who are interested in learning more about this evolving field. (
  • Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid β peptides but not on plaque formation," Journal of Neuroscience , vol. 22, no. 24, pp. 10539-10548, 2002. (
  • Human APOE isoform-dependent effects on brain β -amyloid levels in PDAPP transgenic mice," Journal of Neuroscience , vol. 29, no. 21, pp. 6771-6779, 2009. (
  • Thus, the present invention provides methods of treating cardiac hypertrophy as well as transgenic constructs for preparing transgenic animals. (
  • Although transgenic mice and rats were recently produced by retrovirus transduction of these cells in vitro, with transplantation of the transduced cells into infertile recipients, the difficulty of restoring fertility and preparing recipients using spermatogonial transplantation limits practical application of the technique. (
  • Therefore, we decided to evaluate the in vitro fertilization rate, which turned out to be impaired in the transgenic group. (
  • The antimicrobial function of PG-1 was confirmed in vitro by using fibroblast cells isolated from the transgenic mice but not the WT mice. (
  • Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. (
  • In this article, we describe a transgenic neurological mutation, designated wocko (Wo), which disrupts the development of the inner ear. (
  • The TySV40 transgenic murine tumors represent potentially useful tools for investigations into the biology and metastasis of intraocular neoplasms. (
  • The work has many caveats: only one line of transgenic mice was examined, the mice express both AICD and Fe65, and the expression pattern of the transgenes was not compared to pathology. (
  • Fluorescent calcium sensors in transgenic mice give a real-time readout of neuronal activity. (
  • Our results also reveal the important influence of fluorescent tags on optogenetic probe expression and function in transgenic mice. (
  • Andras Nagy of The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Ontario, has a Web site which discusses the use of fluorescent constructs in transgenic mice ( ). (
  • The "Mouse Models Expressing Fluorescent Proteins or lacZ" list, available on the JAX® Mice Web site at , describes in further detail models which express fluorescent proteins. (
  • Fluorescent transgenic mice. (
  • Impaired relaxation is the main manifestation in transgenic mice expressing a restrictive cardiomyopahty mutation, R193H, in cardiac TnI," American Journal of Physiology , vol. 294, pp. (
  • We report here a new mouse transgenic insertional mutation, cryptorchidism with white spotting (crsp). (
  • Using FISH and genetic analyses, the transgenic insert causing the crsp mutation has been mapped to the distal part of mouse chromosome 5. (
  • The mice express the V337M mutation of human tau that causes the tauopathy FTDP-17 in addition to wildtype mouse tau. (
  • Other mice expressing the stronger P301L tau mutation of FTDP-17 die too young to allow analysis over time. (
  • Here, we describe a new allele at the Fu locus caused by a transgenic insertional mutation, H epsilon 46. (
  • To elucidate pathological roles of the virus in disease, transgenic mice were produced that carry the HTLV-I genome. (
  • The new mice were created using genetic engineering techniques that allow researchers to disable specific genes in an animals genome. (
  • The first involves pronuclear injection, a technique developed and refined by Ralph L. Brinster in the 1960s and 1970s, into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. (
  • This method creates a transgenic mouse and is used to insert new genetic information into the mouse genome or to over-express endogenous genes. (
  • Modeling has been most aggressively pursued in mice, for which the techniques of genetic modification are well developed. (
  • To examine this question, we have used genetic reconstitution experiments in mice. (
  • In a proof-of-principle study, genetic deletion of two genes renders male mice infertile by preventing sperm transport through the vas deferens. (
  • In 1981 the laboratories of Frank Ruddle from Yale University, Frank Costantini and Elizabeth Lacy from Oxford, and Ralph L. Brinster and Richard Palmiter in collaboration from the University of Pennsylvania and the University of Washington injected purified DNA into a single-cell mouse embryo utilizing techniques developed by Brinster in the 1960s and 1970s, showing transmission of the genetic material to subsequent generations for the first time. (
  • Reprogramming cells within live mice yields a new type of induced pluripotent stem cell. (
  • Insertional mutagenesis, induced by microinjection of DNA into fertilized ova to produce transgenic animals, provides a molecular tag that marks the site of the mutational event. (
  • Introduction of foreign DNA into the mouse germ line is considered a major technical advancement in the fields of developmental biology and genetics. (
  • We report here that VavP- Bcl2 transgenic mice, 13 engineered to overexpress Bcl2 in cells of all hematopoietic lineages, are highly predisposed to develop follicular lymphoma. (
  • K5-mTert transgenic mice overexpress telomerase in a wide spectrum of tissues. (
  • The need for additional transforming events, suggested by the low incidence of spontaneous tumors, was further indicated by the high susceptibility of the transgenic animals to injections of low doses of N-methyl-N-nitrosourea, a chemical carcinogen with a thymic tropism. (
  • Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females," Proceedings of the National Academy of Sciences of the United States of America , vol. 95, no. 18, pp. 10914-10919, 1998. (
  • Moreover, these Tg mice showed increased susceptibility to the infection with an intracellular pathogen, blood-stage Plasmodium berghei XAT, which is an irradiation-induced attenuated substrain of P. berghei NK65, presumably due to the decreased IFN-γ production. (
  • Studies showed that the K18-hACE2 transgenic mouse infected with a human SARS-CoV strain via intranasal inoculation would not survive. (
  • Three to five days following infection, K18-hACE2 mice began to lose weight and become lethargic with labored breathing. (
  • The team at Texas Biomed, led by Dr. Luis Martínez-Sobrido, Dr. Jordi B. Torrelles and Dr. Joanne Turner, showed detection of virus in the nasal passages, lungs and brain of the K18 hACE2 transgenic mice. (
  • In this study, scientists showed the K18 hACE2 transgenic mice not only succumbed to the infection but showed systemic (multiple organ) infection with significant virus detected in the nasal passages, lungs, and brain - all organs greatly impacted by SARS-CoV-2 in humans. (
  • Microinjection of retrovirus into immature seminiferous tubules resulted in the direct transduction of spermatogonial stem cells in situ, and the animals produced transgenic offspring after mating with females. (
  • Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl. (
  • In contrast, mice with insulin receptor expression limited to brain or liver and pancreatic β cells are rescued from neonatal death, but develop lipoatrophic diabetes and die prematurely. (
  • Increasing the expression of two genes from non-Y chromosomes restores spermatogenesis in male mice that lack Y chromosomes. (
  • age, 5 to 16 mo) from a mouse line transgenic for keratin 14 (K14)-driven LacZ expression and on an outbred Crl:CD1(ICR) background, were identified as having distended abdomens and livers that were diffusely enlarged by numerous cysts (diameter, 0.1 to 2.0 cm). (
  • Several hundreds of transgenic lines with expression of foreign genes specifically targeted to desired organelles/cells/tissues have been characterized. (
  • created transgenic mice in which NF-κB was excessively activated [MIKK (muscle-specific expression of IKK, which is the kinase that phosphorylates the inhibitor, IκB, thus allowing activation of NF-κB) mice] or repressed [MISR (muscle-specific expression of IκB superrepressor) mice], specifically in skeletal muscle. (
  • Future studies are needed to clarify whether the altered fertilization is in fact caused by the high expression of Btc in the transgenic cumulus cells. (
  • Transgenic mice with hematopoietic and lymphoid specific expression of Cre. (
  • Different regions of the heart show specific profiles of Cx expression, which in mouse and human hearts show many similarities, but also some important differences (Table 1 ). (
  • Earlier all the mouse models of the disease relied on an over-expression of alpha-synuclein which was probably caused by a combination of human and mouse genes. (
  • We previously described spontaneous inflammatory AIG in A23 mice, caused by the transgenic expression of the TCR from a Th1 clone, TXA23. (
  • Mice lacking functional expression of Fas ( lpr ) or FasL ( gld ) develop severe autoimmune lymphoproliferative disorders, leading to tissue destruction ( 13 ). (
  • 1993 ) Molecular cloning and characterization of mouse Tie and Tek receptor tyrosine kinase genes and their expression in hematopoietic stem cells. (
  • Moreover, expression of p47 phox and Nox4 in the brain of hRN/hANG-Tg mice also increased. (
  • BAG3 expression increased both in muscle and spinal cord of tg G93A-SOD1 mice at S stage, BAG1 expression increased only in muscle of the same mice. (
  • Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate. (
  • The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. (
  • Our data suggest that the ectopic expression of PG-1 in mice confers enhanced resistance to bacterial infection, laying the foundation for the development of livestock with improved resistance to infection. (
  • Transgenic mouse models now exist that mimic a range of Alzheimer's disease-related pathologies. (
  • He also noticed that severe COVID-19 disease clinical manifestations are very similar to those seen in transgenic laboratory mice created to faithfully mimic human secondary HLH in the lab. (
  • Transgenic mice mimic cardiac hypertrophy. (
  • Though the requirement of PrP C in disease pathogenesis is known, the function of PrP C in nondiseased tissue remains enigmatic because Prnp 0/0 mice exhibit only subtle or disputed phenotypic deficits, arguing that PrP C is largely dispensable for proper neuronal function ( 3 ). (
  • The data published so far show that APOE*3-Leiden mice exhibit severe hypercholesterolemia when they are fed a high-fat/high-cholesterol (HFC) diet. (
  • However, due to structural differences in mouse ACE2 compared to human ACE2 proteins, the SARS coronaviruses exhibit poor tropism characteristics for mouse tissues and are inefficient at infecting mice. (
  • When maintained on a high-saturated fat diet lacking essential fatty acids or a high-carbohydrate, no-fat diet, the Omega mice exhibit high tissue levels of both omega-6 and omega-3 fatty acids, with a ratio of ∼1∶1. (
  • Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. (
  • These mice develop a severe cardiomyopathy and exhibit a significantly shorter life span than do their nontransgenic littermates. (
  • What makes these mice particularly interesting, say the researchers, is that they exhibit sex differences in the development of cardiac hypertrophy similar to those in humans. (
  • Transgenic mouse lines were established that routinely develop these tumors, and they should provide a valuable resource for studies involving cardiac and bone physiology and neoplasia. (
  • These mice have increased sensitivity to developing carcinogen-induced tumors, and by using this mouse strain instead of conventional ones, reductions can be made in both timelines and the number of animals required. (
  • These mice have a higher incidence of both induced and spontaneous tumors, resulting in increased mortality during the first year of life. (
  • After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. (
  • Characterization of intraocular tumors arising in transgenic mice. (
  • Intracamerally transplanted transgenic tumors metastasized from the eyes to the livers of nude mice. (
  • CONCLUSIONS: In TySV40 transgenic mice, intraocular tumors develop that arise at the choroid-RPE interface, and they display morphologic and ultrastructural features consistent with RPE carcinomas. (
  • However, the transgenic tumors express melanoma-associated antigens and a propensity to metastasize to the liver, two features characteristic of uveal melanomas. (
  • Photoreceptor cell tumors in transgenic mice. (
  • RESULTS: All mice produced developed either ocular or intracranial tumors, or both, at an early age. (
  • One line of mice was generated, and all mice of this line develop both retinal photoreceptor cell and pineal tumors by as early as 2 weeks of age. (
  • Researchers aim to look at the muscle atrophy and muscle sparing in the transgenic mice. (
  • A transgenic mouse company is paying researchers who mention its animal models in scientific papers. (
  • Researchers develop mouse lines to help them see whether the maternal or paternal X chromosome is inactivated. (
  • Texas Biomed researchers were among the first to discover that this transgenic mouse succumbs to infection, which are critical learnings for future studies. (
  • The earliest signs of Parkinson's disease can seemingly be displayed by the first transgenic mouse created by UCSF researchers. (
  • Researchers at NIH have generated transgenic mice in which the M3 muscarinic receptor is overexpressed in pancreatic beta cells. (
  • Fleischer led the research effort working with postdoctoral researchers Hong-Bo Xin, who helped initiate the knock-out mouse project, and later with Deng-Sheng Cheng. (
  • Strikingly, these mutant mice were resistant to diet-induced glucose intolerance and hyperglycemia. (
  • Pimplikar and colleagues show that transgenic mice overexpressing AICD develop tau pathology, neurodegeneration, and a measurable defect in working memory. (
  • In summary, these mice might enable a more detailed observation of how tau pathology develops over time than was possible before (See also related news item ). (
  • TRAMP mice characteristically express the T antigen oncoprotein by 8 weeks of age and develop distinct pathology in the epithelium of the dorsolateral prostate by 10 weeks of age. (
  • Insulin receptor and lipid metabolism pathology in ataxin-2 knock-out mice. (
  • I am going to produce a population of transgenic mice using lentiviral transduction methods, using sperm mediated transgenesis where eGFP will be used as reporter. (
  • While that earlier research was done with chimeric chickens, it demonstrated the enormous opportunities that transgenic chickens hold as a therapeutics production system," said Robert Kay, Ph.D. Origen Therapeutics president and chief executive officer. (
  • For this purpose, we used chimeric double transgenic (Tg) mice of the human renin (hRN) and human angiotensinogen (hANG) genes. (
  • The chimeric (hRN/hANG-Tg) mice were produced by mating of hRN-Tg and hANG-Tg mice. (
  • Transgenic mouse models of Alzheimer's disease. (
  • Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P (
  • That raises the question of whether the pathological features seen in AD mouse models arise from AICD, or Aβ, or both. (
  • We have looked at three mouse models so far and we do see increased AICD levels," Pimplikar told ARF. (
  • Mouse models play a critical role in both vaccine and drug development. (
  • This review focuses on the insights gained from transgenic mouse models. (
  • Mouse models have enhanced our understanding of (patho)-physiological implications of Cx diversity in the heart. (
  • Is the Subject Area "Mouse models" applicable to this article? (
  • Taconic Transgenic Models™ (Models) are produced and distributed under rights to patents and intellectual property licensed from various institutions. (
  • Genetically very similar to the human species, mice play an important role in biomedical research and have served as experimental models for a wide variety of pathologies, including cancer, cardiovascular diseases, and behavioral disorders. (
  • Scientists have not previously had access to mouse models for SARS-CoV-2 infection studies, because typical lab mice are not susceptible to this virus. (
  • He is also involved in creating mouse models of the disease that can help in developing therapies. (
  • In contrast, autoantigen-specific Th2 T cell clones, when transferred to T cell-deficient mice, lead to the development of disease in both insulin-dependent diabetes and EAE models ( 8 , 9 ). (
  • Examples of behavioral tasks successfully applied to transgenic and knockout mouse models are provided, as well as references to the primary literature and step-by-step methods protocols. (
  • 8, 9 ] Transgenic animals with alterations of the growth hormone axis are promising models of brain structure, function, and age-related changes relevant to all of these interventions. (
  • The present paper discusses the current achievements of modeling neuron loss in transgenic mouse models based on APP/A β and Tau overexpression and provides an overview of currently available AD mouse models showing these pathological alterations. (
  • Identification of the underlying mutations opened manifold opportunities for the generation of transgenic mouse models. (
  • A variety of different transgenic AD mouse models have been developed during the last 15 years which can be categorized as either APP single transgenic mice (e.g. (
  • We have extensive experience and a strong track record in the design of mouse models for neuronal diseases such as Alzheimer's , Parkinson's , retinitis or encephalomyelitis , behavioral disorders such as autism , schizophrenia , depression or anxiety , and other research fields like epilepsy , stress , pain , taste or thermoreception . (
  • We have extensive experience and a strong track record in the design of mouse models for inflammatory diseases such as hepatitis, nephritis or inflammatory bowel disease, autoimmune diseases such as systemic lupus erythematosus, joint disorders such as arthritis, allergy , and infections such as cholera, hepatitis, leishmaniasis or chlamydial infection. (
  • Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. (
  • Genetically modified mice are used extensively in research as models of human disease. (
  • The disease symptoms and potential drugs or treatments can be tested against these mouse models. (
  • In the developing mouse hippocampus, intrinsic neuronal excitability does not alter CA3 neuron development but regulates spine formation and synaptic transmission in CA1 neurons. (
  • For instance, photoablation of lacZ -expressing cells has been used conditionally to kill postmitotic neurons in transgenic mice but requires direct access to the tissue for illumination ( Nirenberg and Cepko, 1993 ). (
  • As 11-month-old adults, the V337M mice have aggregations of phosphorylated human tau predominantly in neurons of the CA1, CA2, and CA3 areas of hippocampus. (
  • Takashima's team also reports weakened neural activity in the hippocampi of their transgenic mice, which they attribute to a smaller number of functional neurons, as well as impaired performance in two rodent behavioral tests. (
  • Analysis of 17-month-old APP 751SL /PS1M146L transgenic mice using unbiased stereologic methods revealed a loss of CA1-3 neurons in a magnitude of ~30% compared to age-matched PS1 control animals. (
  • The implantation of the Btc transgenic mice was delayed, but this was not the reason for the litter size reduction, because the mean number of total embryos either attached or recovered from the uterus of transgenic females was already markedly reduced when compared to the number of embryos present in the uterus of control females. (
  • We show that combined restoration of insulin receptor function in brain, liver, and pancreatic β cells rescues insulin receptor knockout mice from neonatal death, prevents diabetes in a majority of animals, and normalizes adipose tissue content, lifespan, and reproductive function. (
  • These mice reveal that the NF-κB is clearly responsible for at least one pathway that leads to muscle wasting but does not appear to be a central regulator of insulin sensitivity in muscle. (
  • RESULTS- In euglycemic, insulin-resistant L1 mice, we detected hyperadiponectinemia with normal levels of adiponectin receptor-1 and -2. (
  • Thus, in mice in which insulin signaling is restricted to liver, selected regions of the brain and pancreatic β-cells (referred to as L1) are, surprisingly, resistant to insulin's direct effect on HGP ( 18 ). (
  • Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin. (
  • For example, in the NOD mouse, administration of β cell autoantigens (insulin, glutamic acid decarboxylase, or IA-2) protects from diabetes through the induction of Th2 cytokines ( 6 ), an effect not observed in IL-4 o/o mice ( 7 ). (
  • The resulting mice show a pronounced increase in glucose tolerance and enhanced plasma insulin levels. (
  • Transgenic mice overexpressing human G972R IRS-1 show impaired insulin action and insulin secretion. (
  • We found that Tg972 mice developed age-related glucose and insulin intolerance and hyperglycaemia, with insulin levels comparatively low. (
  • Glucose utilization and insulin signalling were impaired in all key insulin target tissues in Tg972 mice. (
  • Under a high-fat diet, Tg972 mice had increased body and adipose tissue weight, and were more prone to develop diet-induced glucose and insulin intolerance. (
  • A mouse has been genetically engineered to have increased muscle growth and strength by overexpressing the insulin-like growth factor I (IGF-I) in differentiated muscle fibers. (
  • Mice were given about 25mg of seed meal in suspension, containing transgenic pea, nontransgenic pea, or bean, twice a week for 4 weeks. (
  • The life span of bmyf5 mice was significantly shortened, with an average life span of 109 days, compared with at least a twofold longer life expectancy for nontransgenic littermates. (
  • They used transgenic and nontransgenic litter mates - so the article may describe how they sorted the mixed population of eGFP expressing mice. (
  • In Tg(PrP,ΔGPI) mice, disease onset could be accelerated either by inoculation with brain homogenate prepared from spontaneously ill animals or by coexpression of membrane-anchored, full-length PrP C . In contrast, coexpression of N-terminally truncated PrP(Δ23-88) did not affect disease progression. (
  • Remarkably, disease from ill Tg(PrP,ΔGPI) mice transmitted to mice expressing wild-type PrP C , indicating the spontaneous generation of prions. (
  • Bradley, A, van der Weyden, L. (2006) Mouse: Chromosome Engineering for Modeling Human Disease. (
  • Disease resistance in DQ6 transgenic mice was associated with reduced synthesis of anti-AChR IgG, IgG2b, and IgG2c Ab's and reduced IL-2 and IFN-γ secretion by H-AChR- and peptide α320-337-specific lymphocytes. (
  • While minor differences in weight fluctuation were noted between male and female mice after infection, the study did not indicate that gender played a major role in SARS-CoV-2 infectivity or disease progression. (
  • This study is the first to identify the amount of virus necessary during an initial exposure for the transgenic mice to develop severe COVID-19 disease. (
  • A proportion of A51 mice spontaneously develop AIG by 10 wk of age, with a disease characterized by eosinophilic infiltration of the gastric mucosa and Th2 differentiation of transgenic T cells in the gastric lymph node. (
  • Autoimmune gastritis (AIG) is commonly observed in d3Tx BALB/c mice and resembles the human disease pernicious anemia, in that the effector T cells and autoantibodies recognize the α and β subunits of the gastric parietal cell H/K-ATPase ( 11 , 12 ). (
  • VavP- Bcl2 mice also had a propensity to develop kidney disease of the autoimmune type. (
  • The ability to readily create transgenic chickens through this technology, and then to scale up production through conventional breeding further adds to the practicality of this technology for large-scale production of therapeutic proteins. (
  • The investigators then would be able to visualize the conversion of normal tau proteins into prions in live mice, and follow their spread through the brain. (
  • And yet, none of the transgenic proteins that have been commercially approved has been tested. (
  • We call on you to impose an immediate ban on all GM food and feed until proper assessment on the immunogenicity of all the transgenic proteins has been carried out. (
  • Transgenic Pea that Made Mice Ill Raises serious safety concerns on transgenic proteins in general that must be addressed while a ban on all GM food and feed is imposed. (
  • There are indeed important lessons to be learned from the scientific findings [2], which raise serious safety concerns over transgenic proteins in general. (
  • 2004) The knockout mouse project. (
  • The most common type is the knockout mouse, where the activity of a single (or in some cases multiple) genes are removed. (
  • Thus, there are now 3 variables that exist between the 2 main study groups: mouse background strain, inclusion of human knock-in genes, and route of human cell engraftment. (
  • The antigen-binding domains of HLA-DRA and HLA-DRB1*0401 (representative of the DR4 supertype) were attached to the membrane-proximal domains of I-Ed alpha and I-Ed beta (H2-E), respectively, by replacing exon 2 of the mouse genes with exon 2 of the human genes. (
  • Transgenic mice (named "Omega mice") were engineered to carry both optimized fat-1 and fat-2 genes from the roundworm Caenorhabditis elegans and are capable of producing essential omega-6 and omega-3 fatty acids from saturated fats or carbohydrates. (
  • In 1974 Beatrice Mintz and Rudolf Jaenisch created the first genetically modified animal by inserting a DNA virus into an early-stage mouse embryo and showing that the inserted genes were present in every cell. (
  • Other pathologic changes, including vasculitis, degeneration, and necrosis, were found in the extrapulmonary organs of transgenic mice, and viral antigen was found in brain. (
  • The resulting progeny were further intercrossed to generate Insr −/− and Ttr -INSR (L1) mice and Insr +/+ littermates. (
  • These Tg mice did not show any apparent phenotypic difference from control littermates in lymphoid cells. (
  • Here we report on the production of transgenic mice that ectopically expressed PG-1 and compare their susceptibilities to Actinobacillus suis infection with those of their wild-type (WT) littermates. (
  • Of the 126 mice that were challenged with A. suis , 87% of the transgenic mice survived, whereas 31% of their WT littermates survived. (
  • Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. (
  • In older (28-week-old) mice, lung weights were also significantly increased, consistent with congestive heart failure. (
  • 12-14 Our recent article showed that Ang II content is significantly increased in the brain, as well as in plasma, in hRN/hANG-Tg mice, and that activation of the human RAS in the brain is involved in exaggeration of ischemic brain damage attributed partly to enhancement of oxidative stress. (
  • Both LC3 and p62 mRNAs were significantly up-regulated in skeletal muscle of tg G93A-SOD1 mice at S stage (16 weeks). (
  • LPS-induced increases in chymase activity in the heart and skin were significantly greater in Tg than WT mice. (
  • The mice that survived this early lethal period, however, showed significantly reduced lethality rates even though they carried multiple AVMs. (
  • The PG-1 transgenic mice had significantly lower bacterial loads in their lungs and reduced numbers of pulmonary pathological lesions. (
  • These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. (
  • In the present short paper, we summarize the current achievements of modeling neuron loss in transgenic mice based on APP/A β overexpression. (
  • To elucidate the molecular basis of this association, we have induced experimental autoimmune MG (EAMG) in mice transgenic for HLA-DQ8, DQ6, and DR3, and in DQ8×DQ6 and DQ8×DR3 F1 transgenic mice, by immunization with human acetylcholine receptor (H-AChR) in CFA. (
  • Transgenic & Knockout Mice protocols describe step-by-step approaches to producing cell and mice with migration related defects. (
  • how do I run behavioral assays to find out what's wrong with my mouse? (
  • to discover the wealth of mouse behavioral tasks and to get the guidance you need to select the best methods and necessary controls. (
  • Neurodevelopment and Neurodegeneration" discusses mouse behavioral tasks relevant to neurodevelopmental diseases, such as mental retardation and autism, and to neurodegenerative diseases, such as Alzheimers, Parkinsons, Huntingtons, and amyotrophic lateral sclerosis. (
  • Behavioral Phenotyping of Transgenic and Knockout Mice, Second Edition has been written in Dr. Crawley's private capacity, outside of her professional position at the National Institutes of Health. (
  • Spontaneous mutations at the mouse Fused (Fu) locus cause dominant skeletal and neurological defects and recessive lethal embryonic defects including neuroectodermal abnormalities and axial duplications. (
  • In a developmental study, transgenic mice were treated with GCV during the first postnatal week, with evaluation at P19. (
  • One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. (
  • Using simultaneous whole-cell monitoring of ionic currents and Cl-dependent fluorescence, we determined that the apparent EC 50 for Cl i was 46 mM, indicating that this line is appropriate for measuring neuronal [Cl i ] in postnatal mice. (
  • and (3) major hCAR mRNA SVs increase markedly in postnatal livers of hCAR-TG mice, which mimics the ontogeny of CAR mRNA in humans. (
  • Thus, it is possible to estimate cell-type-specific rates of apoptosis by observing the increases in numbers of cells in the bcl-2-overexpressing transgenic mouse. (
  • MISR mice showed resistance to muscle loss caused by either denervation or injection of Lewis lung carcinoma cells. (
  • Further provided are methods of using the transgenic animals of the present invention, or cells isolated therefrom, for the detection of compounds having therapeutic activity toward cardiac hypertrophy. (
  • They found that when Trf1 is eliminated, the mice develop exactly the same symptoms as aplastic anaemia sufferers: bone marrow failure with the corresponding pancytopenia (a reduction in the number of red and white blood cells, as well as platelets). (
  • Previous attempts to culture PGCs from mice and humans produced embryonic germ cells that look and act like embryonic stem cells. (
  • In addition, the Methods indicate that NOG-EXL mice were engrafted via tail vein injection and NSG mice were engrafted via intrahepatic injection of human cells. (
  • Here, we generated a screening assay to mine inducers of Bdnf transcription in neuronal cells, using primary cultures of cortical cells prepared from a transgenic mouse strain, specifically, Bdnf-Luciferase transgenic ( Bdnf-Luc ) mice. (
  • By preserving the alpha 2 and beta 2 domains of mouse MHC class II, interactions with CD4 co-receptors on T cells was preserved. (
  • T cells from DQ8 transgenic mice responded well to three cytoplasmic peptide sequences of H-AChR (α320-337, α304-322, and α419-437), of which the response to α320-337 was the most intense. (
  • CD4 + T cells that lead to autoimmune gastritis (AIG) in BALB/c mice are either Th1 or Th2 cells. (
  • Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. (
  • MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. (
  • Embryonic stem cells that recombine with the genomic DNA are selected for and they are then injected into the mice blastocysts. (
  • The Center for the Advancement of Science in Space (CASIS) obtains tissue samples from mice flown to the International Space Station to support valuable commercial muscle wasting research. (
  • On-orbit operations require the ability to launch and maintain rodents (mice and rats) in a habitat and in some cases also require rodent euthanasia, dissection, and tissue sample preparation and preservation. (
  • The new DNA becomes part of every cell and tissue of the mouse. (
  • Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. (
  • Conclusions -This study shows that in APOE*3-Leiden mice, duration of an HFC diet is associated with (1) a craniocaudal progression of lesion development and (2) an increased complexity of atherosclerotic lesions. (
  • Affected male mice had degenerative testicular lesions, and their sperm was immotile. (
  • Nonpolycystic K14 control male mice bred well, had no testicular lesions, and had appropriate sperm motility. (
  • BAFF was also independently identified as TALL-1 ( 24 ), as THANK, which regulated apoptosis, NF-κB and c-Jun NH 2 -terminal kinase in a human myelocytic cell line ( 25 ), and, more recently, as BlyS, a factor that, when administrated to normal mice, disrupted splenic B and T cell zones and resulted in elevated serum IgM concentrations ( 26 ). (
  • Here we document the age-related patterns in learning ability of TGM and normal mice. (
  • Learning appeared inferior in both genotypes of very young mice but TGM were confirmed to be superior to normal mice upon maturity. (
  • Older TGM, however, showed rapid age-related loss of their exceptional learning, whereas normal mice at 1 year of age showed little change. (
  • Impaired fertility in transgenic mice overexpressing Betacellulin Peptide growth factors regulate many cellular functions by autocrine, paracrine, juxtacrine or endocrine mechanisms. (
  • Some genetically engineered mice harbor unwanted mutations that hitchhike alongside desired modifications, affecting experimental outcomes. (
  • After 18 months, the mice showed neuronal loss in the hippocampus. (
  • The retina of this mouse reveals that the general neuronal plan has been maintained. (
  • Deleterious effects of neuronal accumulation of glycogen in flies and mice. (
  • The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6-12 h, with PON1R192, PON1Q192, and PON1 mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. (
  • Experiments were conducted to determine whether chronic activation of Rac-1 affects blood pressure (BP) and heart rate (HR). Male Rac-CA and control mice were prepared for chronic cardiovascular monitoring using carotid arterial catheters infused with heparinized saline. (
  • Thus, we analyzed in spinal cord and in muscle of transgenic (tg) G93A-SOD1 mice at presymptomatic (PS, 8 weeks) and symptomatic (S, 16 weeks) stages, and in age-matched control mice, whether mutSOD1 differentially modulates relevant PQC players, such as HSPB8, BAG3, and BAG1. (
  • No changes of HSPB8, BAG3, and BAG1 at PS stage (8 weeks) were seen in all tissues examined in tg G93A-SOD1 and control mice. (
  • Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus. (
  • FLC Business Search Transgenic Mice Overexpressing Islet. (

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