Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Mice, Inbred C57BLTransgenes: Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.Disease Models, Animal: 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, Genetically Modified: PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Rats, Transgenic: Laboratory rats that have been produced from a genetically manipulated rat EGG or rat EMBRYO, MAMMALIAN. They contain genes from another species.Promoter Regions, Genetic: 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, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.Crosses, Genetic: 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.Molecular Sequence Data: 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.Thymus Gland: 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.Mice, Inbred CBAReceptors, Antigen, T-Cell, alpha-beta: 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.Molluscum contagiosum virus: A species of MOLLUSCIPOXVIRUS causing skin lesions in humans. It is transmitted by direct contact or from non-living reservoirs (fomites), such as books or clothing.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.T-Lymphocytes: 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, Messenger: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Clonal Deletion: 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.Mice, Knockout: 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.B-Lymphocytes: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Mice, Inbred DBAReceptors, Antigen, T-Cell: 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.Epitopes, T-Lymphocyte: 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.Immune Tolerance: 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.Antigens, Polyomavirus Transforming: 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.Green Fluorescent Proteins: 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.CD4-Positive T-Lymphocytes: 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.Lymphocyte Activation: 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.Mice, Inbred BALB CPhenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Papillomavirus E7 Proteins: 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.Immunization: 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).Gene Expression Regulation: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Brain: 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, Cultured: 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.Hybridomas: 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.Mutation: 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.Immunoglobulin kappa-Chains: One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Flow Cytometry: 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.Amino Acid Sequence: 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.DNA Primers: 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.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Freeze Substitution: A modification of the freeze-drying method in which the ice within the frozen tissue is replaced by alcohol or other solvent at a very low temperature.T-Lymphocytes, Cytotoxic: 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.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Antigens, CD4: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Membrane Proteins: 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.Nuclear Receptor Subfamily 4, Group A, Member 3: An orphan nuclear receptor that is closely related to members of the thyroid-steroid receptor family. It was originally identified in NERVE CELLS, however it may play regulatory roles in a variety of other tissues.Neurons: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antigens, CD: 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.Tobacco: A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.Polymerase Chain Reaction: 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.CD8-Positive T-Lymphocytes: 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.Signal Transduction: 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.Interferon-gamma: 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.Cytotoxicity, Immunologic: 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.Nuclear Proteins: 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.Interleukin-4: 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.Peptides: 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, Monoclonal: Antibodies produced by a single clone of cells.Plants, Toxic: Plants or plant parts which are harmful to man or other animals.Tumor Cells, Cultured: 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.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Plant Proteins: 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, Reporter: 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.Gene Expression Regulation, Developmental: 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 Fusion Proteins: 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.Arabidopsis: 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.Amyloid beta-Protein Precursor: 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.Luminescent Proteins: 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.Plant Leaves: 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)Transformation, Genetic: 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.Integrases: 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.Genetic Engineering: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Alzheimer Disease: 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)Lac Operon: 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.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Amyloid beta-Peptides: 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.Oryza sativa: 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.Genetic Vectors: 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.Blotting, Western: 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.Zebrafish: 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.Genes, Plant: The functional hereditary units of PLANTS.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Blotting, Southern: 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.beta-Galactosidase: 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.Seeds: 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.Encephalitis Virus, California: A species in the ORTHOBUNYAVIRUS genus of the family BUNYAVIRIDAE. Serotypes are found in temperate and arctic regions and each is closely associated with a single species of vector mosquito. The vertebrate hosts are usually small mammals but several serotypes infect humans.Meninges: The three membranes that cover the BRAIN and the SPINAL CORD. They are the dura mater, the arachnoid, and the pia mater.Myocardium: 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.In Situ Hybridization: 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.Plant Diseases: Diseases of plants.Apoptosis: 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.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.Doxycycline: A synthetic tetracycline derivative with similar antimicrobial activity.Mice, Inbred Strains: 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.Solanum tuberosum: A plant species of the genus SOLANUM, family SOLANACEAE. The starchy roots are used as food. SOLANINE is found in green parts.Mammary Glands, Animal: MAMMARY GLANDS in the non-human MAMMALS.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Hyperplasia: 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.DNA-Binding Proteins: 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.Chromosomes, Artificial, Bacterial: 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.Nerve Tissue ProteinsGlucuronidaseCloning, Molecular: 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.Blotting, Northern: 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.Tissue Distribution: 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.Keratin-14: 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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Embryo, Mammalian: 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.Homeodomain Proteins: 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).Up-Regulation: 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.Plant Roots: 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)Agrobacterium: A genus of gram negative, aerobic, rod-shaped bacteria found in soil, plants, and marine mud.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.Gene Targeting: 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, Genetically Modified: Organisms whose GENOME has been changed by a GENETIC ENGINEERING technique.Mammary Tumor Virus, Mouse: 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.Strelitziaceae: A plant family of the order ZINGIBERALES, subclass Zingiberidae, class Liliopsida. Some species in this genus are called bird-of-paradise which is also a common name for CAESALPINIA and Heliconia (HELICONIACEAE).Lycopersicon esculentum: A plant species of the family SOLANACEAE, native of South America, widely cultivated for their edible, fleshy, usually red fruit.DNA: 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).Animals, Newborn: Refers to animals in the period of time just after birth.tau Proteins: 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).Metallothionein: 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.Transfection: 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.Huntington Disease: 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)DNA, Complementary: 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.Mice, Inbred C3HCell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Epidermis: 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).Superoxide Dismutase: 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 1.15.1.1.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Cardiomegaly: 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.Keratins: 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.Caulimovirus: 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.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.DNA, Plant: Deoxyribonucleic acid that makes up the genetic material of plants.Chimera: An individual that contains cell populations derived from different zygotes.Droughts: Prolonged dry periods in natural climate cycle. They are slow-onset phenomena caused by rainfall deficit combined with other predisposing factors.Papilloma: 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)Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Vaccines, Edible: 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.Organ Size: The measurement of an organ in volume, mass, or heaviness.Amyotrophic Lateral Sclerosis: 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)Plasmids: 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.Globins: A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Islets of Langerhans: 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.Nerve Degeneration: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Muscle, Skeletal: 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.Growth Hormone: 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.RNA, Plant: Ribonucleic acid in plants having regulatory and catalytic roles as well as involvement in protein synthesis.Gossypium: 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.Maze Learning: 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)Agrobacterium tumefaciens: 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.Mammary Neoplasms, Animal: Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).Down-Regulation: 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, Artificial, Yeast: 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.Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.RNA Interference: 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.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Genes, ras: 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.Disease Progression: 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.Neoprene: An oil-resistant synthetic rubber made by the polymerization of chloroprene.Immunoblotting: 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.Tauopathies: 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.Uvea: The pigmented vascular coat of the eyeball, consisting of the CHOROID; CILIARY BODY; and IRIS, which are continuous with each other. (Cline et al., Dictionary of Visual Science, 4th ed)Genes, myc: 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.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Gene Dosage: 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, Fluorescence: 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.Heart: The hollow, muscular organ that maintains the circulation of the blood.Repressor Proteins: 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.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.RNA: 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)Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Proto-Oncogene Proteins: 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.Behavior, Animal: The observable response an animal makes to any situation.Adoptive Transfer: 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 ...
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 ...
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
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 ...
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 - http://www.scopus.com/inward/record.url?scp=0028041963&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0028041963&partnerID=8YFLogxK. 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.. ...
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 [https://dx.doi.org/10.1007/s00401-015-1486-0 ...
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 ...
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
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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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 ...
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 ...
We have previously described the production and characterization of GK gene locus transgenic mice (56). These mice express and regulate a single additional copy of the entire GK gene locus; thus, they provide a model for determining the effect of a modest increase in GK gene expression in preventing or limiting glycemic control impaired by high-fat feeding. Because GK expression was twofold higher in the liver but lower in pancreatic β-cells when compared with that in nontransgenic control mice, we concluded that an overexpression of the GK transgene in the liver was primarily responsible for the hypoglycemic phenotype of these animals (56).. At 6 weeks of age, the body weight of the GK transgenic mice (20.9 ± 1.0 g) was not different from the nontransgenic animals (21.6 ± 1.3 g) (Fig. 1). Feeding of a normal Rodent Chow diet caused the body weight of the transgenic and control animals to increase to 33.1 ± 1 and 35 ± 3 g, respectively, by the 30th week. The BMI at the 30th week did not ...
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 ...
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
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
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 ...
Principal Investigator:NISHIMURA Yasuharu, Project Period (FY):1989 - 1991, Research Category:Grant-in-Aid for Developmental Scientific Research., Research Field:Immunology
Much has been learned in recent years concerning the nature of tumor antigens recognized by T cells. To apply this knowledge clinically, the nature of the host response to individual and multiple tumor antigens has to be characterized. This will help to define the efficacy of immune surveillance and the immune status of the host following exposure to tumor antigens expressed on pre-neoplastic tissue. To approach these questions, we have developed a transgenic mouse which expresses the tumor-specific antigen P91A. The single amino acid substitution in P91A results in the expression of a new MHC class I (H-2Ld)-binding peptide. In transgenic tissue, the H-2Ld/P91A complex is expressed in isolation from other tumor-associated antigens, allowing definition of the immune response to a single defined tumor antigen, a situation closely analogous to events during tumorigenesis. We show that CD8+ T cell immune surveillance of P91A is ineffective without the introduction of a helper determinant operating ...
We have made use of T cell receptor (TCR)-transgenic mice with CD4+ T cells expressing a receptor specific for the self-antigen C5 (fifth component of complement) to study the role of different antigen-presenting cells in the determination of CD4+ T cell effector type. Contact of T cells from C5 TCR-transgenic mice with C5 protein or C5 peptide in vivo or in vitro induces biased T helper cell (Th) 1 type responses resulting in exclusive production of high levels of interferon gamma and interleukin (IL) 2. Transgenic mice, in contrast to nontransgenic littermates, do not generate an antibody response to C5. We show in this paper that B cell presentation in vitro induces a switch to the Th2 subset indicated by production of IL-4, and targetting C5 to B cells in vivo results in the generation of C5-specific antibodies. ...
PHILADELPHIA - A new appreciation for the interplay between two cell nucleus proteins that lead both intertwined and separate lives is helping researchers better understand fatty liver disease, according to a new study by researchers at the Perelman School of Medicine at the University of Pennsylvania. They published their findings this month in Genes & Development.. The liver normally makes and stores fat, which is required in moderation for normal body function. However, excess fat can cause major liver damage. In fact, fatty liver is a leading cause of liver failure in the United States and is often brought on by obesity and diabetes.. "We showed that simply deleting the protein HNF6 in liver cells of adult transgenic mice fed normal laboratory chow leads to fatty liver syndrome," said senior author Mitchell Lazar, MD, PhD , director of the Institute Diabetes, Obesity, and Metabolism. "Although HNF6 is known mainly as an activator of protein transcription, loss of it upregulates many ...
Human herpesvirus 6 (HHV-6) is widely spread in the human population and has been associated with several neuroinflammatory diseases, includingmultiple sclerosis. To develop a small animal model of HHV-6 infection, we analyzed the susceptibility of several lines of transgenic mice, expressing human CD46, identified as a receptor for HHV-6. We showed that HHV-6A (GS) infection results in the expression of viral transcripts in primary brain glial cultures from CD46-expressing mice, while HHV-6B (Z29) infection was inefficient. HHV-6A DNA persisted for up to 9 months in the brain of CD46-expressing mice but not in the non-transgenic littermates, whereas HHV-6B DNA levels decreased rapidly after infection in all mice. Persistence in the brain was observed only with infectious but not heat-inactivated HHV-6A. Immunohistological studies revealed the presence of infiltrating lymphocytes and monocytes in periventricular areas of the brain of HHV-6A-infected mice. Furthermore, HHV-6A stimulated the ...
Design The authors used transgenic mice in which the Hh receptor Patched1 (Ptch1) could be conditionally inactivated in a body-wide manner and mice in which Gli1 could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR.. ...
Constitutive expression of the TXA51 TCR in a large proportion of developing and mature T cells results in AIG of indolent phenotype, characterized by late onset of disease, pathological eosinophilia in the gastric mucosa, and elaboration of Th2 cytokines. The A51 transgenic mice represent a unique model for autoimmune disease, and they illustrate that the in vivo response to a self-Ag can be Th2 and yet also result in pathological autoimmunity. This model of Th2-mediated organ-specific autoimmune disease provides an important example that challenges the simple view that Th2 responses are necessarily protective, whereas Th1 responses are pathogenic (32). Indeed, all other known TCR-transgenic models for autoimmune diseases suggest that Th1 responses are required for pathogenicity. This Th2 model suggests that there is a narrow window of T cell activation by self Ags, dictated by the TCR itself, in which autoimmune reactivity may coexist with a distinct cytokine phenotype.. The pathogenicity of ...
In this report, we show that overexpression of scurfin in FoxP3 Tg mice results in the inability to mount an effective humoral immune response. FoxP3 Tg mice displayed lower levels of circulating IgG when compared with their nontransgenic littermates, and had a dramatically reduced response when challenged with a specific Ag. However, B cells from FoxP3 Tg mice produced normal levels of Ig when stimulated in vitro, suggesting that a defect in T cell-derived help was responsible for the phenotype seen in these mice. Three additional lines of evidence support this hypothesis. First, T cells from FoxP3 Tg mice failed to provide help to B cells from NLC mice. Second, CD4+ T cells from FoxP3 Tg mice failed to up-regulate CD40L and CD69 expression when stimulated. Finally, significantly fewer IL-4- and IFN-γ-producing splenic T cells were generated in immunized FoxP3 Tg mice as compared with NLC mice. Overall, these findings suggest that the poor Ag-specific Ab response generated by FoxP3 Tg mice ...
Crossing of transposase and transposon transgenic mice yields experimental mice in which the transposon is mobilizing in the soma due to the presence of both transposase and transposons. Singly transgenic littermates serve as controls. Crossing T2/Onc2 transgenics to Rosa26SB11 transgenics resulted in 5.6% to 12.5% doubly transgenic offspring depending on the T2/Onc2 concatomer used. The observed sub-Mendelian ratio of genotypes was due to high rates of embryonic lethality in double transgenics. All T2/Onc2;Rosa26SB11 mice that survived to birth were moribund by 114 days of age. Twenty-three of 24 mice developed hematopoietic malignancies (mainly T-cell lymphoma) and 2 mice developed medulloblastomas. In addition to frank neoplasia, 4 mice also had hyperplasia of the intestine or pituitary gland ( 15). These results contrast to experiments using the lower-copy T2/Onc concatomers and CAGGS-SB10 transposase in which doubly transgenic mice had life spans comparable with controls. Although somatic ...
STOP cassette - posted in Molecular Biology: Hi all, I plan to generate a new transgenic mouse where gene expression is prevented by upstream floxed STOP cassette: -promoter-loxP-STOP-loxP-transgene- Upon crossing to a CRE-recombinase expressing mouse line the STOP will be removed, leading to transgene expression. Does anyone know of nay studies demonstrating the efficiency of different STOP sequences/cassettes? There are at least a couple of them at Addgene and apparently some more in...
Increased KAI1 levels in AICD transgenic mice. (A) The AICD transgenic mice, but not the control or Fe.27 mice, show expression of KAI1 gene. Membrane fractions
The experiments described in this thesis document the development of two in vivo models, to investigate the effect of competition for peptide-MHC and factors independent of MHC on T cell proliferation, differentiation, generation of memory cells and affinity maturation. The first model made use of 3 strains of T cell receptor (TCR) transgenic (tg) mice of varying specificity for antigen-MHC class II. To determine the effect of antigen specific and non-specific competition on the early stages of the T cell response, the efficiency with which naïve antigen-specific CD4+ T cells were recruited into an ongoing immune response was investigated. Recruitment into cell division and cytokine production was shown to decrease with an increasing time delay between two cell cohorts of the same specificity, leading to a significant drop in recruitment with a delay of only 24 hours. Injection of additional antigen could partially compensate for this decrease, suggesting that lack of available antigen limited ...
Sequences within the first intron of the alpha 1(I) collagen gene have been implicated in the regulation of expression of alpha 1(I) collagen-reporter gene constructs in cultured cells. However, the physiological significance of these intronic elements has not been established. We have used in situ hybridization to examine whether a cell-specific pattern of expression of human alpha 1(I) collagen-human growth hormone minigenes exists in transgenic mice. Our results indicate that transgenes which contained 2,300 bp of promoter/5 flanking sequence and an intact first intron were well expressed by fibroblasts in dermis and fascia, whereas transgenes lacking the intronic sequence, +292 to +1440, were not expressed in dermis and poorly expressed in fascia. Analysis of transgene expression in cultured fibroblasts obtained from dermal explants of transgenic animals confirmed the requirement for these intronic sequences in the regulation of the alpha 1(I) collagen gene. In contrast, transgenes with or ...
Penn State and Agariger, Inc. have patented the technology of making new transgenic mushrooms, which have increased hope of using mushrooms for the mass
Ins-TOPGAL and Ctnnb1 C429S mutant mice. Ctnnb1 C429S mutant mice were generated by ENU mutagenesis. C492S homozygous mutant mice are infertile. Ins-TOPGAL transgenic mice are useful for visualizing Wnt signal pathway. The transgene contains the nLacZ gene under the control of a TOPFLASH promoter (6x TCF binding motifs upstream of a TK promoter). The transgene construct was flanked by the insulator core elements ...
We previously found that transgenic mice overexpressing MMTV-FLAG-hPAD2 (PAD2OE) developed spontaneous skin lesions, with a subset of these lesions progres
Transgenic mice and methods of preparing such mice are disclosed. The mice exhibit decreased platelet counts and/or megakaryocyte leukemia.
Paschen, A.*, Song, M.*, Osen, W*., Nguyen, X. D., Mueller-Berghaus, J., Fink, D., Daniel, N., Donzeau, M., Nagel, W., Kropshofer, H. and Schadendorf, D.,Detection of spontaneous CD4+ T-cell responses in melanoma patients against a tyrosinase-related protein-2-derived epitope identified in HLA-DRB1*0301 transgenic mice. Clin Cancer Res 2005. 11: 5241-5247. Osen, W., Soltek, S.*, Song, M.*, Leuchs, B., Steitz, J., Tuting, T., Eichm ller, S. B., Nguyen, X. D., Schadendorf, D. and Paschen, A., Screening of human tumor antigens for CD4 T cell epitopes by combination of HLA-transgenic mice, recombinant adenovirus and antigen peptide libraries. PLoS One 2010. 5: e14137.. Gardyan, A.*, Osen, W.*, Zornig, I., Podola, L., Agarwal, M., Aulmann, S., Ruggiero, E., Schmidt, M., Halama, N., Leuchs, B., von Kalle, C., Beckhove, P., Schneeweiss, A., Jager, D. and Eichm ller, S. B., Identification of NY-BR-1-specific CD4(+) T cell epitopes using HLA-transgenic mice. Int J Cancer 2015. 136: 2588-2597.. Hao, S., ...
|i|Cre|/i| expression in these transgenic mice can be seen in the embryo and in adult endothelium of developing and quiescent vessels, as well as in a subset of hematopoietic cells. When bred with mice carrying a |i|loxP|/i|-flanked sequence of interest, Cre-mediated recombination will result in deletion of the flanked genome. These mice may be useful in studies of the cardiovascular system.
[Cloning of the DNA fragment of a transgenic mouse containing an integrated recombinant plasmid].: The plasmid rescue method has been used to isolate the reco
The researchers instead embarked on creating Cre-loxP conditional knock out mice for Ezh2. The technique involves two transgenic mouse strains, one carries Cre, an enzyme, under the control of a B or T cell promoter gene. The other strain, in this case, carries the Ezh2 gene surrounded by a special binding site called "loxP". LoxP sites on DNA are recognizable by the Cre enzyme. When Cre mice are bred with mice carrying the loxP surrounded Ezh2 gene, the resulting mice lack Ezh2 gene only in developing B cells. As a result the Ezh2 needed in embryonic development is not deterred in these mice. This in vivo model of studying cell signaling is invaluable ...
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Animal studies. Esrrg- and Esrrb-floxed (ERRγ/ERRβL2/L2) mice were generated at the Mouse Clinical Institute in Strasbourg according to a strategy previously described (44) and back-crossed to the C57BL/6JBomTac background for 10 generations. To generate mice with skeletal muscle-specific deletions of the ERRγ/ERRβ alleles (herein referred to as ERRβ/γ dmKO mice), ERRγ/ERRβL2/L2 mice were crossed to human skeletal actin-Cre (HSA-Cre) mice. PPARα-null (Ppara-/-) mice in the C57BL/6J background were purchased from The Jackson Laboratory (stock no. 008154). High-expressing (HE) MCK-PPAR mice have been previously described (16, 17). C3B6F1 MCK-miR-499 mice (19) were bred with MCK-PPARα mice to generate the MCK-PPARα/miR-499 double-transgenic mice. The MCK-PPARα mice are in a C57BL/6J pure strain and MCK-PPARβ/δ mice are in a hybrid B6/CBA background, with the following specific exceptions: hybrid MCK-PPAR mouse lines were used in Figure 3 (C3/B6) and Supplemental Table 1 (B6/CBA). NTG ...
Sigma-Aldrich offers abstracts and full-text articles by [Chun-Yan Wang, Wei Zheng, Tao Wang, Jing-Wei Xie, Si-Ling Wang, Bao-Lu Zhao, Wei-Ping Teng, Zhan-You Wang].
Cardiac fibroblasts (CF) are required for normal cardiac function and are important in various diseases. A limitation of the field is the lack of suitable transgenic lines that allow for genetic manipulation of CF in vivo. By comparing the transcriptomes of defined cardiac cell types, a candidate promoter was identified and used to generate a transgenic mouse line for CF-specific transgenesis (Ccdc80-Cre). Cell type-specificity and targeting efficiency were characterized in comparison to a transgenic line previously employed for the targeting of fibroblasts in other organs. « ...
transgenic: Of, relating to, or being an organism whose genome has been altered by the transfer of a gene or genes from another species or breed: transgenic mice; transgenic plants.
Background. Transgenic animal technology includes the process of inserting functional foreign genes into animals and using them as a tool to research intricate biological processes. Transgenic Animals are animals that have DNA introduced into their cells artificially. These animals become important instruments in exploring regulation of various genetic pathways, gene expression* and cellular processes. By inserting a gene into a live organism, scientists can explore the function of this gene in various environments. Transgenic animals serve a variety of different functions, proving them to be powerful research tools.Transgenic animals can serve as distinctive models for disease, and are made specifically to answer precise biological questions. ...
Several super immunodeficient models expressing cytokines designed to drive myeloid cell lineage commitment have been generated. The most advanced cytokine transgenic mouse models are the huNOG-EXL, NSG-SGM3 and the MISTRG. This group of models has promise to improve human immune system engraftment in mice, but each one has different features which must be considered when choosing an experimental model.
Transgenic models refer to genetically modified organisms in which the genome has been altered for deletion, insertion/amplification, or substitution.
PolyGene guarantees rapid generation of genetically modified rodent models, such as mice and rats. We are specialized in genome editing via CRISPRs to generate gene knockouts and knock-ins.
To get rid of any type of confusion, view this page of myhomeworkhelp.com and learn what transgenics homework help team has to offer.
Mouse RELM-α Recombinant produced in E.Coli is a monomeric, non-glycosylated, polypeptide chain containing 88 amino acids and having a molecular mass of 10 kDa.
091011 - Animais Transg nicos: Conceito, Metodologias e Aplica es - Transgenic animals: concept, methodologies and applications | Veterinaria.org . La primera comunidad veterinaria de habla hispana con presencia en Espa a y Am rica del Sur.
Cancer is a class of diseases in which a group of cells displays uncontrolled growth and invasion that destroys adjacent tissues, and sometimes send metastasis to other locations in the body. When one is interested in cancer research, mice will be the preferred animal. Murine models of cancer include transplantable models, spontaneous and autochthonous models, human tumor xenografts, orthotopic models, models of metastasis and transgenic tumor models.
Transgenic Organisms. HOOK. HOOK. What is a TRANSGENIC Organisms?. Lets break apart the word: Trans = Genic = Organism = Transgenic Organisms are: It is an organism that has had genes inserted (or moved into) from a different organism Slideshow 2661807 by astrid
Feature :. B-cell specific expression of PrP on a prnp knockout background (Expression vector pHT4-YK 12 under the control of the Igk promoter). ...
Examining the molecular mechanisms and pathogenesis of cancer using traditional approaches, such as transgenic mice, to model human cancers as well as new technology, such as DNA Chip microarrays, to identify and characterize key proteins involved in the process of tumor initiation and progression. ...
Did you know that it’s possible to write multiple lines in an Excel cell? You can type Enter without necessarily having to move to the...
مقاله ISI انگلیسی شماره 78876 - ترجمه نشده - موضوع : الگوریتم های تکاملی - 10 صفحه - سال انتشار : 2014 - منبع : الزویر ساینس دایرکت
Comprising over 20,000 different lines, Clipsal prides itself on being the most advanced and skilled in the Australian electrical industry, providing the market with the most technologically advanced electrical solutions ...
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 ...
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 ...
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 ...
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 ...
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 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 ...
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 ...
BioAssay record AID 299827 submitted by ChEMBL: Drug level in Tg2576 betaAPP swedish transgenic mouse brain at 500 umol/kg, sc twice a day for 5 days.
The findings of Massaad and colleagues will advance our basic understanding of the neuroprotective role of mitochondrially targeted antioxidants in Alzheimer disease (AD) pathogenesis. Their findings suggest that mitochondrial superoxide dismutase 2 (SOD2) decreases hippocampal superoxide radicals, ameliorates learning/memory deficits, and decreases amyloid-β (Aβ) plaques in double transgenic mice that overexpress SOD2 and mutant human amyloid precursor protein. Interestingly, they also found a decreased ratio of Aβ1-42 to 1-40 in double transgenic mice. These findings further support the mitochondrial oxidative damage hypothesis of AD, and may have important implications for mitochondrially targeted antioxidant therapeutics in AD.. Increasing evidence suggests that mitochondrial abnormalities are involved in the development and progression of AD (reviewed in Reddy, 2009). Further, it has been proposed that mitochondrially generated free radicals and oxidative damage are involved in abnormal ...
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Roberts, Jenna, "Characterization of a cellular hyperplasia in a mutant transgenic mouse." (1989). Summer and Academic Year Student Reports. 885 ...
As has been described in naturally occurring CAA (1, 5), vascular amyloid deposition in APP23 mice is most frequently found in arteries/arterioles and occurs most often in vessels outside the brain parenchyma proper (e.g., pia, fissures). The arterial predilection suggests that an anatomical difference between arteries and veins (e.g., presence of significant amounts of smooth muscle) could contribute to the development of CAA. Indeed, it has been hypothesized that Aβ is deposited by vascular smooth muscle cells and/or perivascular microglia, and APP expression and Aβ production by vascular cells have been well documented (22, 23). These reports and the observation that vessels apart from the neuropil are more often affected strongly implicate local production or circulating Aβ as an important source, although these hypotheses fail to explain the exclusive localization of CAA to cerebral vessels. In the present study, through examination of APP transgenic mice on an App-null background, we ...
Friedreichs ataxia (FRDA) is the most common hereditary ataxia in the caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia, hypertrophic cardiomyopathy and increased incidence of diabetes. FRDA is caused by impaired expression of the FXN gene coding for the mitochondrial protein frataxin. During the past ten years, the development of mouse models of FRDA has allowed better understanding of the pathophysiology of the disease. Among the mouse models of FRDA, the liver conditional mouse model pointed to a tumor suppressor activity of frataxin leading to the hypothesis that individuals with FRDA might be predisposed to cancer.. Read More: Clinical data and characterization of the liver conditional mouse model exclude neoplasia as a non-neurological manifestation associated with Friedreichs ataxia. ...
Tau is a microtubule stabilizing protein that forms aggregates in Alzheimers disease (AD). Tau derived from AD patients brains induces tau aggregation in a prion-like manner when injected into susceptible mouse models. Here we investigated whether cerebrospinal fluid (CSF) collected from patients diagnosed with probable AD or mild cognitive impairment (MCI) likely due to AD harbors a prion-like tau seeding potential. CSF was injected intrahippocampally into young P301S tau transgenic mice. CSF obtained from AD or MCI patients increased hippocampal tau hyperphosphorylation and tau tangle formation in these mice at 4 months post-seeding. Tau pathology was also accentuated in the contralateral hippocampus, and in anterior and posterior directions, indicative of spreading. We provide first evidence for in vivo prion-like properties of AD patients CSF, accelerating tau pathology in susceptible tau transgenic mice. This demonstrates that biologically active tau seeds reach the CSF compartment in AD.
Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p<0.01); resistance to ...
Motor neuron disease is clinically characterized by progressive muscle wasting leading to total muscle paralysis. A long history of pathological study of patients has firmly established that the primary lesion site is in spinal and cortical motor neurons. In addition to the wide-spread loss of these neurons, neuronal abnormalities including massive accumulation of neurofilaments in cell bodies and proximal axons have been also widely observed, particularly in the early stages of the disease. To test whether high accumulation of neurofilaments directly contributes to the pathogenic process, transgenic mice that produce high levels of neurofilaments in motor neurons have been generated. These transgenic mice show most of the hallmarks observed in motor neuron disease, including swollen perikarya with eccentrically localized nuclei, proximal axonal swellings, axonal degeneration and severe skeletal muscle atrophy. These data indicate that extensive accumulation of neurofilaments in motor neurons ...
TY - JOUR. T1 - Interleukin-6 regulates the expression of hypothalamic neuropeptides involved in body weight in a gender-dependent way. AU - Señarís, R. M.. AU - Trujillo, M. L.. AU - Navia, B.. AU - Comes, G.. AU - Ferrer, B.. AU - Giralt, M.. AU - Hidalgo, J.. PY - 2011/8/1. Y1 - 2011/8/1. N2 - Interleukin (IL)-6 has been involved in the control of body weight and body fat. Nevertheless, the mechanisms underlying these effects are not completely understood because central and peripheral actions of IL-6 are plausible. To gain further insight into the central effects of IL-6, we used transgenic mice expressing the IL-6 gene under the control of the glial fibrillary acidic protein (GFAP) promoter (GFAP-IL-6 mice), therefore with central nervous system-restricted over-expression of IL-6, and we studied the expression of the main neuropeptides responsible for energy homeostasis in specific hypothalamic nuclei. Neuropeptide Y (NPY), agouti-related peptide (AgRP), melanin-concentrating hormone ...
TY - JOUR. T1 - Clinical characteristics of familial amyotrophic lateral sclerosis with Cu/Zn superoxide dismutase gene mutations. AU - Abe, Koji. AU - Aoki, M.. AU - Ikeda, M.. AU - Watanabe, M.. AU - Hirai, S.. AU - Itoyama, Y.. PY - 1996. Y1 - 1996. N2 - We report clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with 4 different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene, that result in amino acid substitutions of histidine46 by arginine (H46R), leucine84 by valine (L84V), isoleucine104 by phenylalanine (I104F), and valine148 by isoleucine (V148I), in 5 Japanese families. Although features of progressive neurogenic muscular atrophy were common in patients of these families, patients of each family showed characteristic clinical features. FALS patients with the H46R mutation showed a benign clinical course and stereotype progression of muscular weakness and atrophy beginning from the legs. In FALS with the L84V mutation, ...
Background The TNF superfamily member B lymphocyte stimulator (BLyS), referred to as BAFF, is known to be an effective modulator of peripheral B cell homeostasis that promotes B cell survival and differentiation. BLyS is expressed by a few stromal cells, T cells, and most myeloid cell. BLyS transgenic mice show an expansion of the peripheral mature B cell compartment, hyperglobulinemia, anti-single-stranded DNA and anti-double-stranded DNA antibodies, and circulating immune complexes. A proliferation-inducing ligand (APRIL) is a homolog to BLyS that is expressed by monocytes, macrophages, DCs, T cells, and others. APRIL is virtually undetectable in normal tissues but is strongly expressed in adenocarcinomas and can accelerate the growth of malignant cells in vitro and in vivo. APRIL/BLyS heterotrimers are present in the serum of patients with systemic autoimmune diseases like rheumatoid arthritis (RA), SLE, and SS. APRIL over expression promotes a strong survival signal for both CD4+ and CD8+ T ...
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 ...
"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 ...
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 ...
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 ...
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:". "Entrez Gene: TGFA transforming growth factor alpha". Ojeda, S. R.; Ma, Y. J.; Rage, F. (September ...
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 ...
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. ...
Sawicki also generates transgenic mice. Using this technology, she has developed several cancer mouse models useful for her ... Chen, Y; Megosh, LC; Gilmour, SK; Sawicki, JA; O'Brien, TG (2015-09-28). "K6/ODC transgenic mice as a sensitive model for ... "Evidence for expression of the paternal genome in the two-cell mouse embryo". Nature. 294: 450-451. 1981-12-03. doi:10.1038/ ... Sawicki, JA; Rothman, CJ (2015-09-28). "Evidence for stem cells in cultures of mouse prostate epithelial cells". Prostate. 50: ...
in IL-10 transgenic mice. or dosing with IL-10 leads to control of primary tumor growth and decreased metastatic burden. More ... A study in mice has shown that IL-10 is also produced by mast cells, counteracting the inflammatory effect that these cells ... Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. and, ... Over time a more nuanced picture of IL-10's function has emerged as treatment of tumor bearing mice has been shown to inhibit ...
Two successful approaches have been identified: transgenic mice and phage display. As of November 2016, thirteen of the ... Lonberg N, Huszar D (1995). "Human antibodies from transgenic mice". Int. Rev. Immunol. 13 (1): 65-93. doi:10.3109/ ... who market their TRIANNI Mouse platform. Ablexis, LLC - who market their AlivaMab Mouse platform. Phage display can be used to ... human monoclonal antibody therapeutics on the market were derived from transgenic mice technology. Adopting organizations who ...
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" (PDF). Journal of Biological Chemistry. 288 (6): 4056-65. ... 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- ... "Lithium Treatment Arrests the Development of Neurofibrillary Tangles in Mutant Tau Transgenic Mice with Advanced ...
Koike S, Choji T, Takeshi K, Shinobu A, Iku I, Hiromichi Y (1991). "Transgenic Mice Susceptible to Polio Virus". Proceedings of ... 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 ...
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- ...
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 ...
Mice do not have a granulysin homolog, but transgenic mice expressing human granulysin have been engineered. Granulysin has ... Huang LP, Lyu SC, Clayberger C, Krensky AM (January 2007). "Granulysin-Mediated Tumor Rejection in Transgenic Mice". J. Immunol ... 2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci ...
Joyce C, Freeman L, Brewer HB, Santamarina-Fojo S (2004). "Study of ABCA1 function in transgenic mice". Arterioscler. Thromb. ... 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 ... "Mouse PubMed Reference:". Luciani MF, Denizot F, Savary S, Mattei MG, Chimini G (May 1994). "Cloning of two novel ABC ...
Wolfer, D. P. (2002). "J.N. Crawley: What's wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice". Genes ... What's wrong with my mouse: Behavioral phenotyping of transgenic and knockout mice, Wiley-Interscience, Hoboken, NJ (2007) 523 ... Behavioral Phenotyping of Transgenic and Knockout Mice". Genes, Brain and Behavior. 7 (7): 831-831. doi:10.1111/j.1601-183X. ... especially mice. Early in her career, she developed the dark-light mouse exploration test, and showed that it is a valid test ...
Husain-Krautter, S; Kramer, JM; Li, W; Guo, B; Rothstein, TL (2015). "The osteopontin transgenic mouse". Clinical Immunology. ...
Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. „Science". 274 (5284), s. 99-102, 10 1996 ... Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. „Nature". 373 (6514), s. ... Simon A.S.A. James Simon A.S.A. i inni, Iron, Copper, and Zinc Concentration in Aβ Plaques in the APP/PS1 Mouse Model of ... and motor coordination in female APP23 transgenic mice with the Swedish mutation. „Brain Research (journal)". 956 (1), s. 36-44 ...
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 ...
... and sudden death in ACE2 transgenic mice with downregulated connexins (англ.) // Journal of Molecular and Cellular Cardiology ( ...
Transgenic Mice at Amazon - Low Prices on Transgenic Mice. Ad amazon.co.uk/Transgenic Mice Low Prices on Transgenic Mice. Free ... Inducible transgenic mouse models. - The University of Michigan Inducible transgenic mouse models allow for the activation of ... Inducible Transgenic Mouse Models , SpringerLink Inducible transgenic mouse models allow for the activation of and the lac and ... Tetracycline Inducible Transgenic Mice. Transgenic Mice - Customized Knockout/Knockin Models. Ad Customized Knockout/Knockin ...
... these transgenic mice tend to have an increased number of reticulocytes in peripheral blood; consistent with some degree of ... we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver ... Transgenic fetuses with high-copy numbers of the transgene suffer severe anemia and die before birth. Using a construct with ... Thus, these mice have mild anemia. These results are discussed with relation to the coordinate regulation of alpha- and beta- ...
... The Digitized Atlas of Mouse Liver Lesions. Transgenic mice carrying an albumin promoter linked to ... An aged uPA transgenic mouse with an hepatocellular adenoma. There is evidence of toxic hepatopathy in the adjacent hepatic ... AL-TAg x AL-myc Dual Transgenic * Unique Lesions of Genetically Altered Mice ... A large and a small nodule of regenerating hepatocytes in an Alb-uPA transgenic mouse. ...
... Wolfgang Schechinger hubahopp at gmx.de Sat Dec 11 17:26:32 EST 2004 *Previous message: Transgenic ... Previous message: Transgenic Mice Advice? *Next message: Transgenic Mice Advice? * Messages sorted by: [ date ] [ thread ] [ ...
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Tg(PrP,ΔGPI) mice were crossed with mice expressing wt PrP to generate Tg mice expressing PrP(ΔGPI) and wt PrPC; these mice ... Prnp0/0 mice and injected them intracerebrally into weanling Tg8015/Prnp0/0 mice or Tg(PrP)4053 mice overexpressing wt mouse ... Prion infectivity from Tg8015/Prnp0/0 mice transmitted not only to Tg4053 mice but also to Tg8015/Prnp0/0 mice. The serial ... 8015/9949 mice. These Tg8015/9949 mice developed CNS dysfunction at 572 d, which was similar to that of Tg8015/Prnp0/0 mice at ...
... including 10 NASA mice, and 10 CASIS mice. The CASIS mice include 16 week-old C57Bl female mice, 5 wild type and 5 transgenic ... Muscle Atrophy of Muscle Sparing in Transgenic Mice (Rodent Research-1 (CASIS)) - 11.22.16. Overview , Description , ... A total of 10 mice, 5 wild type and 5 transgenic, are sent to the ISS to live in microgravity for 21 days. ... Researchers aim to look at the muscle atrophy and muscle sparing in the transgenic mice. ...
Thymic lymphomas in interleukin 9 transgenic mice.. Renauld JC1, van der Lugt N, Vink A, van Roon M, Godfraind C, Warnier G, ... Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo ... of transgenic mice developed thymic lymphomas at the age of 3-9 months. The tumor cells, which were clonal, with unique T cell ... was much more efficiently transplanted into transgenic than in normal mice. Moreover, the in vitro proliferative activity of ...
Spontaneous generation of anchorless prions in transgenic mice.. Stöhr J1, Watts JC, Legname G, Oehler A, Lemus A, Nguyen HO, ... To model GSS, we generated transgenic mice expressing cellular prion protein (PrP(C)) lacking the glycosylphosphatidyl inositol ... E-P) Neuropathologic analysis of ill Tg8015/Prnp0/0 (E, F, I, J, M, and N) and Tg4053 mice (G, H, K, L, O, and P); ... Remarkably, disease from ill Tg(PrP,ΔGPI) mice transmitted to mice expressing wild-type PrP(C), indicating the spontaneous ...
... G. Chen,1,2 Y. Li,2 J. Tian,1 L. Zhang,1 P. Jean- ... Y. Li, P. Y. J. Charles, C. Nan et al., "Correcting diastolic dysfunction by Ca2+ desensitizing troponin in a transgenic mouse ... J. Du, J. Liu, H. Z. Feng et al., "Impaired relaxation is the main manifestation in transgenic mice expressing a restrictive ... Q. Q. Huang, H. Feng, J. Liu et al., "Troponin T heterogeneity in transgenic mouse ventricular muscle results in cardiomyopathy ...
Transgenic APP[V717I] Mice. Transgenic mice (n = 4) were treated with BL (1 mg/kg) from weaning (age, 3 weeks) for 17 weeks. In ... transgenic mice. In a follow-up study using the APP[V717I]/PS1[A246E] AD transgenic mice, bryostatin significantly reduced the ... transgenic mice. In a more recently developed AD double-transgenic mouse, bryostatin was effective in reducing both brain Aβ40 ... Transgenic mice APP[V717I]/PS1[A246E]: Mortality. (A) Life table analysis of all mice. Both treated (n = 23) and untreated (n ...
A transgenic mouse company is paying researchers who mention its animal models in scientific papers. ... Fluorescent calcium sensors in transgenic mice give a real-time readout of neuronal activity. ... Researchers develop mouse lines to help them see whether the maternal or paternal X chromosome is inactivated. ... Scientists make mice strains with multiple mutations in less than a month without using embryonic stem cells. ...
Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface ... We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the ... Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was ... transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 ...
Mice. Transgenic mice expressing the human APOE*3-Leiden gene were generated and bred with C57Bl/6J females as described ... mice received standard mouse chow for 9 months. To label DNA-synthesizing cells, 6 transgenic animals of the 6-month diet group ... Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. J Biol Chem. 1993;268:10540-10545. ... Atherosclerosis in APOE*3-Leiden Transgenic Mice. From Proliferative to Atheromatous Stage. Esther Lutgens, Mat Daemen, Mark ...
It would be interesting to cross the FE65 single-transgenic mice to conventional APP-transgenic mouse models to see whether ... The work has many caveats: only one line of transgenic mice was examined, the mice express both AICD and Fe65, and the ... The observed behavioral deficits in the AICD-transgenic mice as compared to wild-type mice are small, but the neurodegeneration ... In transgenic mice overexpressing both AICD and Fe65, they find phosphorylation and redistribution of tau in young (four-month- ...
We have generated mice transgenic for a bcr/abl p190 DNA construct and find that progeny are either moribund with, or die of ... Acute Leukaemia in bcr/abl Transgenic Mice Nature. 1990 Mar 15;344(6263):251-3. doi: 10.1038/344251a0. ...
The foreign DNA is put into the nucleus of a fertilized mouse egg. ... Mice that have had DNA from another source put into their DNA. ... transgenic mice listen (trans-JEH-nik...) Mice that have had ... The new DNA becomes part of every cell and tissue of the mouse. These mice are used in the laboratory to study diseases. ... The foreign DNA is put into the nucleus of a fertilized mouse egg. ...
We have used transgenic mouse technology to establish immortalized hepatoma cell lines stably secreting heterologous proteins, ... Novel cell lines derived from transgenic mice expressing recombinant human proteins. Transgenic hepatoma-derived cell lines ... transgenic mice trans-immortalization hepatocyte α1-antitrypsin factor IX onc gene ... We have used transgenic mouse technology to establish immortalized hepatoma cell lines stably secreting heterologous proteins, ...
... of a single transgeniclacZ transgenic mouse, which served as a control (Fig.5 a), and the double transgenic lacZ-TK mouse (Fig ... Generation of transgenic mice. We generated transgenic mice expressing the herpes TK gene under the control of a human GFAP ... nlacZ transgenic mice. a, Central lobule of cerebellum from nlacZ transgenic mouse (control) treated with GCV at P3. b, Central ... Cerebella of nontransgenic mice were treated with GCV at P1 [a, e, i, m (column 1)], or transgenic mice were treated at either ...
ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimers-like neuropathology," ... Introducing Human APOE into Aβ Transgenic Mouse Models. Leon M. Tai,1 Katherine L. Youmans,1 Lisa Jungbauer,1,2 Chunjiang Yu,1 ... K. R. Bales, F. Liu, S. Wu et al., "Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice," ... K. R. Bales, F. Liu, S. Wu et al., "Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice," ...
Crossing the MIKK mice to MuRF-/- mice showed partial rescue of the muscle-wasting phenotype of the MIKK mice. MISR mice showed ... The MIKK mice exhibited profound muscle loss, and crossing the MIKK mice to the MISR mice reversed this phenotype. Several ... created transgenic mice in which NF-κB was excessively activated [MIKK (muscle-specific expression of IKK, which is the kinase ... NF-κB Promotes Muscle Wasting in Transgenic Mice Message Subject. (Your Name) has forwarded a page to you from Science ...
Child Receives Transgenic Skin Over Most of His Body. By Ruth Williams , November 8, 2017 ... Boosting levels of a the immunosuppressive protein PD-L1 in blood stem cells halts diabetes in a mouse model of the disease. ... Infectious protein aggregates from the skin of human patients can cause disease in mice. ... tags: transgenic mice x disease/medicine x The Scientist. » transgenic mice and disease/medicine ...
A handful of transgenic mouse strains exist that express various forms of tau, but they either die at a young age or differ ... transgenic mice with the deletion of lysine at position 280 would show early and extensive PHF formation, as this in vitro work ... Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau. J Neurosci. 2002 Jan 1;22(1):133-41. ... Transgenic Mice Accumulate Human Tau in Degenerating Hippocampal Neurons. Quick Links. *Article ...
Control mice indicates female nontransgenic mice; Lp(a) transgenic mice, female Lp(a) transgenic mice; Control gene, right ... transgenic mice were created by the mating of human apo(a) transgenic mice and human apoB transgenic mice.13,26-28⇓⇓⇓ Human apo ... The background of both mice was FVB mice. Lp(a) transgenic mice were created by breeding of both homotransgenic mice and ... transgenic mice. In Lp(a) transgenic mice, serum Lp(a) concentration was much higher in female mice (52.5±6.3 mg/dL, n=10) than ...
Research Sheds Light on Simulating Alzheimers Disease in Transgenic Mice. by Kathy Jones on September 7, 2013 at 9:31 PM ... showed that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in mice ...
  • Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the endogenous mouse alpha-globin genes. (ox.ac.uk)
  • Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. (ox.ac.uk)
  • Using a construct with both the human alpha- and beta-globin genes and the beta-globin DCR, live mice with low-copy numbers were obtained. (ox.ac.uk)
  • Both human globin genes are expressed at high levels in adult red cells to give human hemoglobin HbA in amounts equal to or greater than endogenous mouse hemoglobin. (ox.ac.uk)
  • Metabolic labeling experiments showed balanced mouse globin synthesis, but imbalanced human globin synthesis, with an alpha/beta biosynthetic ratio of approximately 0.6. (ox.ac.uk)
  • An important goal of the research community is to translate information gained from studying transgenic mouse models into useful clinical applications. (aacrjournals.org)
  • 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. (nih.gov)
  • Alzheimer-type neuropathology in transgenic mice overexpressing V717F β -amyloid precursor protein," Nature , vol. 373, no. 6514, pp. 523-527, 1995. (hindawi.com)
  • 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. (biomedsearch.com)
  • To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of Abeta in deposits, i.e., human and/or mouse, we performed a histopathological analysis, using mouse and human specific antibodies, of the neocortex and hippocampus in 6, 12 and 19 months old APP/PS1 double and APP and PS1 single transgenic mice. (unboundmedicine.com)
  • For example, transgenic mice containing additional copies of the amyloid precursor protein (APP) gene, have been useful in producing the Aß deposition characteristic of AD and DS, but not the cytoskeletal changes that are the hallmarks of these human disorders. (springer.com)
  • 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. (hindawi.com)
  • 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. (jneurosci.org)
  • Although numerous molecular insights were gained from the analysis of these transgenic malignant tumors, the early events leading to malignant transformation have not been systematically investigated nor has the biological potential of hyperplastic lesions been documented. (aacrjournals.org)
  • 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. (jci.org)
  • Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus. (genetics.org)
  • Reprogramming cells within live mice yields a new type of induced pluripotent stem cell. (the-scientist.com)
  • 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. (hindawi.com)
  • 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. (hindawi.com)
  • Increasing the expression of two genes from non-Y chromosomes restores spermatogenesis in male mice that lack Y chromosomes. (the-scientist.com)
  • In a proof-of-principle study, genetic deletion of two genes renders male mice infertile by preventing sperm transport through the vas deferens. (the-scientist.com)
  • Palmiter RD, Chen HY and Brinster RL (1982) Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. (springer.com)
  • 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. (sciencemag.org)
  • A recent study published in the Neural Regeneration Research (Vol. 8, No. 24, 2013) showed that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in mice carrying mutant amyloid-β precursor protein and presenilin-1 genes. (medindia.net)
  • 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. (taconic.com)
  • The transgene and several skeletal muscle-specific genes were expressed only in patchy areas of the heart in heterozygous mice. (ahajournals.org)
  • 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. (ahajournals.org)
  • For this purpose, we used chimeric double transgenic (Tg) mice of the human renin (hRN) and human angiotensinogen (hANG) genes. (ahajournals.org)
  • The new mice were created using genetic engineering techniques that allow researchers to disable specific genes in an animals genome. (bio-medicine.org)
  • Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. (wikipedia.org)
  • In 1974 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. (wikipedia.org)
  • This method creates a transgenic mouse and is used to insert new genetic information into the mouse genome or to over-express endogenous genes. (wikipedia.org)
  • 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. (wikipedia.org)
  • Transgenic mice expressing mutant forms of Rab27a, a GTPase that has been implicated in the pathogenesis of choroideremia, were generated. (bmj.com)
  • To investigate the involvement of Rab27 in degenerative retinal diseases and other diseases where Rab27a might play a role, we generated transgenic mice overexpressing mutant forms of Rab27a. (bmj.com)
  • On the FVB genetic background, homozygous transgenic animals fed a high-fat diet ate 10% more and were 12% heavier at 13 weeks of age than wild-type animals, and they had higher systemic leptin levels. (jci.org)
  • Previous attempts to culture PGCs from mice and humans produced embryonic germ cells that look and act like embryonic stem cells. (rxpgnews.com)
  • The panel recommended that diagnostic nomenclature of transgenic lesions in mice be based on similar morphological, immunohistochemical, and biological criteria so that direct comparisons among mouse models and with humans would be possible. (aacrjournals.org)
  • 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. (bio-medicine.org)
  • and (3) major hCAR mRNA SVs increase markedly in postnatal livers of hCAR-TG mice, which mimics the ontogeny of CAR mRNA in humans. (ovid.com)
  • Therefore, we decided to evaluate the in vitro fertilization rate, which turned out to be impaired in the transgenic group. (uni-muenchen.de)
  • 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. (nih.gov)
  • 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. (jimmunol.org)
  • In some Alb-uPA mice there is complete loss of the transgene, and these mice eventually develop hepatocellular adenomas and carcinomas. (nih.gov)
  • 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. (arvojournals.org)
  • To elucidate pathological roles of the virus in disease, transgenic mice were produced that carry the HTLV-I genome. (sciencemag.org)
  • 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. (google.com)
  • 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 ). (asm.org)
  • 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. (ovid.com)
  • A genetically modified mouse (Mus musculus) is a mouse that has had its genome altered through the use of genetic engineering techniques. (wikipedia.org)
  • The first involves pronuclear injection into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. (wikipedia.org)
  • We have used transgenic mouse technology to establish immortalized hepatoma cell lines stably secreting heterologous proteins, such as human α 1 -antitrypsin and human factor IX. (springer.com)
  • Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl. (jci.org)
  • 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 (jci.org)
  • 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. (genetics.org)
  • A genomic probe from the wild-type H epsilon 46 locus detected a transcript that is disrupted by the transgenic insertion, representing a candidate for the wild-type allele of Fused. (genetics.org)
  • The corneal lesion observed in T27aT15 mice most closely resembles posterior polymorphous corneal dystrophy and might result from the disruption of the equivalent mouse locus. (bmj.com)
  • 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 ). (rupress.org)
  • Here we document the age-related patterns in learning ability of TGM and normal mice. (chiro.org)
  • Learning appeared inferior in both genotypes of very young mice but TGM were confirmed to be superior to normal mice upon maturity. (chiro.org)
  • Older TGM, however, showed rapid age-related loss of their exceptional learning, whereas normal mice at 1 year of age showed little change. (chiro.org)
  • 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. (pnas.org)
  • Remarkably, disease from ill Tg(PrP,ΔGPI) mice transmitted to mice expressing wild-type PrP C , indicating the spontaneous generation of prions. (pnas.org)
  • 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 ). (pnas.org)
  • In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. (ahajournals.org)
  • 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. (jci.org)
  • 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. (jimmunol.org)
  • 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 ). (jimmunol.org)
  • 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 ). (jimmunol.org)
  • VavP- Bcl2 mice also had a propensity to develop kidney disease of the autoimmune type. (bloodjournal.org)
  • A mouse model that closely models the human disease would, therefore, be of significant benefit. (bloodjournal.org)
  • Mice culled at 344 and 468 d had clinical prion disease. (cdc.gov)
  • The mouse culled at 720 d had clinical prion disease. (cdc.gov)
  • Two mice with clinical prion disease were culled at 558 and 749 d. (cdc.gov)
  • All mice had clinical prion disease. (cdc.gov)
  • 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. (pubmedcentralcanada.ca)
  • Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease. (genoway.com)
  • 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. (genoway.com)
  • The use of transgenic disease models in biomedicine promises to dramatically accelerate the development of new human diagnostic and therapeutic treatments. (bmj.com)
  • This proto-oncogene has been overexpressed in a mouse model of the disease in order to explore the role of MYCN in this tumour. (bmj.com)
  • In contrast, Tg mice expressing OvPrP with valine (V) at 136 (OvPrP-V136) infected with the same prions developed disease rapidly, and the converted prion was comprised of an unstable (U), diffusely distributed conformer. (nih.gov)
  • Percent (%) affected mice refers to numbers of mice within an inoculated cohort manifesting progressive clinical signs associated with prion disease. (nih.gov)
  • To directly investigate the therapeutic potential of DCR3 in preventing this disease, we generated transgenic nonobese diabetic mice, which overexpressed DCR3 in beta cells. (sigmaaldrich.com)
  • Genetically modified mice are used extensively in research as models of human disease. (wikipedia.org)
  • The disease symptoms and potential drugs or treatments can be tested against these mouse models. (wikipedia.org)
  • 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. (uni-muenchen.de)
  • 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. (sigmaaldrich.com)
  • The transgenic islets had a higher transplantation success rate and survived for longer than wild-type islets. (sigmaaldrich.com)
  • 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. (springer.com)
  • In addition, the direct product of β-secretase cleavage, C99, has toxic or pathogenic effects in cultured cells and in transgenic mice ( 28 , 29 ). (pnas.org)
  • MISR mice showed resistance to muscle loss caused by either denervation or injection of Lewis lung carcinoma cells. (sciencemag.org)
  • 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. (google.com)
  • 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). (news-medical.net)
  • 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. (nature.com)
  • 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. (jci.org)
  • CD4 + T cells that lead to autoimmune gastritis (AIG) in BALB/c mice are either Th1 or Th2 cells. (jimmunol.org)
  • 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. (bloodjournal.org)
  • 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. (rupress.org)
  • By preserving the alpha 2 and beta 2 domains of mouse MHC class II, interactions with CD4 co-receptors on T cells was preserved. (taconic.com)
  • These Tg mice did not show any apparent phenotypic difference from control littermates in lymphoid cells. (jimmunol.org)
  • We now report that MT-Exendin mice develop extensive tissue lymphocytic infiltration with increased numbers of CD4 + and CD8a + cells in the liver and/or kidney and increased numbers of B220 + cells present in the pancreas and liver. (diabetesjournals.org)
  • For example, cell-based delivery using cells genetically engineered to produce a DPP-4-resistant GLP-1 analog has demonstrated persistent improvements in glucose control after implantation of GLP-1-producing cells into diabetic mice ( 10 ). (diabetesjournals.org)
  • MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. (rupress.org)
  • Embryonic stem cells that recombine with the genomic DNA are selected for and they are then injected into the mice blastocysts. (wikipedia.org)
  • 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. (jimmunol.org)
  • Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA. (ovid.com)
  • 27 neuroblastomas from hemizygous transgenic mice and 4 tumours from homozygous mice were examined histologically, and Ki67 and MYCN immunocytochemistry performed in 24 tumours. (bmj.com)
  • A total of 10 mice, 5 wild type and 5 transgenic, are sent to the ISS to live in microgravity for 21 days. (nasa.gov)
  • 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. (sciencemag.org)
  • 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. (uni-muenchen.de)
  • Insulin-stimulated glucose uptake in skeletal muscle was increased by twofold in Syn4 transgenic mice compared with wild-type mice as assessed by hyperinsulinemic-euglycemic clamp analysis, consistent with a twofold increase in insulin-stimulated GLUT4 translocation in skeletal muscle. (diabetesjournals.org)
  • Currently, 3 carcinogenicity packages have been initiated, with 2 preliminary 5/28-day studies in rasH2 wild-type mice already completed. (criver.com)
  • The avoidance rate in wild-type mice gradually increased. (ahajournals.org)
  • The number of activated microglia in the spinal cord of transgenic mice was significantly higher than that of wild-type mice, suggesting that inflammation might be observed in the spinal cord of transgenic mice. (pubmedcentralcanada.ca)
  • Here, we found that the hNEDL1-Tg mice exhibited decreased locomotor activity compared with wild-type mice and developed ALS-like symptoms, including motor neuron degeneration, decreased axon, and microglia activation in the lumbar spinal cord and muscle weakness. (pubmedcentralcanada.ca)
  • Tissue homogenates from doxycycline-treated or untreated bitransgenic mice (BT) were tested for β-galactosidase activity by chemiluminescence and compared with values obtained from wild-type (WT) mice. (asnjournals.org)
  • Background activity of kidney lysates from wild-type mice was subtracted from measured activity to yield specific activity. (asnjournals.org)
  • FVB, wild type mice. (nih.gov)
  • Even basic issues like choosing the correct "wild-type" control mouse to use for comparison are sometimes overlooked. (wikipedia.org)
  • Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome," American Journal of Physiology , vol. 289, no. 3, pp. (hindawi.com)
  • In a developmental study, transgenic mice were treated with GCV during the first postnatal week, with evaluation at P19. (jneurosci.org)
  • 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. (ovid.com)
  • 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. (frontiersin.org)
  • Eye abnormality in T27aT15 mice results from random insertional mutagenesis of the transgene as it was only observed in one line. (bmj.com)
  • 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. (ahajournals.org)
  • Affected male mice had degenerative testicular lesions, and their sperm was immotile. (ingentaconnect.com)
  • Nonpolycystic K14 control male mice bred well, had no testicular lesions, and had appropriate sperm motility. (ingentaconnect.com)
  • TXA23, a Th1 cell, induces, on transfer to nu/nu mice, a severe gastritis characterized by a lymphocytic infiltrate and autoantibody production. (jimmunol.org)
  • ATXN2-CAG42 sequesters PABPC1 into insolubility and induces FBXW8 in cerebellum of old ataxic knock-in mice. (genoway.com)
  • 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. (dana.org)
  • Cancer Center investigators benefit from the cost-effective services of the Transgenic Mouse/ES Cell Shared Resource focusing on the generation, maintenance and long-term storage of germline-altered mice. (vicc.org)
  • As a consequence, many investigators are now utilizing the powerful tools of transgenic technology to address some of these questions. (textbookx.com)
  • MT-Exendin mice express proexendin-4 mRNA in multiple tissues and process the proexendin-4 precursor to Ex-4, resulting in detectable circulating levels of bioactive Ex-4 ( 11 ). (diabetesjournals.org)
  • Glucose utilization and insulin signalling were impaired in all key insulin target tissues in Tg972 mice. (sigmaaldrich.com)
  • the results shown are the mean of tissues derived from two mice. (asnjournals.org)
  • Impaired fertility in transgenic mice overexpressing Betacellulin Peptide growth factors regulate many cellular functions by autocrine, paracrine, juxtacrine or endocrine mechanisms. (uni-muenchen.de)