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Mice, TransgenicMice, Inbred C57BLTransgenesDisease Models, AnimalPlants, Genetically ModifiedGene ExpressionRats, TransgenicPromoter Regions, GeneticAnimals, Genetically ModifiedCrosses, GeneticMolecular Sequence DataThymus GlandMice, Inbred CBAReceptors, Antigen, T-Cell, alpha-betaH-2 AntigensImmunohistochemistryT-LymphocytesRNA, MessengerBase SequenceClonal DeletionMice, KnockoutB-LymphocytesSpleenMice, Inbred DBAReceptors, Antigen, T-CellEpitopes, T-LymphocyteImmune ToleranceAntigens, Polyomavirus TransformingGreen Fluorescent ProteinsCD4-Positive T-LymphocytesLymphocyte ActivationMice, Inbred BALB CPhenotypePapillomavirus E7 ProteinsImmunizationGene Expression RegulationCell DifferentiationBrainCells, CulturedHybridomasMutationImmunoglobulin kappa-ChainsPeptide FragmentsFlow CytometryAmino Acid SequenceDNA PrimersAutoantigensCancer VaccinesT-Lymphocytes, CytotoxicT-Lymphocyte SubsetsAntigens, CD4Reverse Transcriptase Polymerase Chain ReactionLiverCell DivisionMembrane ProteinsImmunoglobulin GNeuronsMembrane GlycoproteinsCell LineAutoantibodiesAntigens, CDTobaccoPolymerase Chain ReactionCD8-Positive T-LymphocytesSignal TransductionInterferon-gammaCytotoxicity, ImmunologicNuclear ProteinsCytokinesInterleukin-4PeptidesAntibodies, MonoclonalPlants, ToxicTumor Cells, CulturedGene Expression Regulation, PlantOrgan SpecificityPlant ProteinsGenes, ReporterGene Expression Regulation, DevelopmentalRecombinant Fusion ProteinsArabidopsisAmyloid beta-Protein PrecursorLuminescent ProteinsPlant LeavesTransformation, GeneticIntegrasesGenetic EngineeringTranscription FactorsAlzheimer DiseaseLac OperonPlaque, AmyloidAmyloid beta-PeptidesOryza sativaGenetic VectorsBlotting, WesternZebrafishGenes, PlantEnhancer Elements, GeneticBlotting, Southernbeta-GalactosidaseSeedsArabidopsis ProteinsGene Transfer TechniquesMyocardiumIn Situ HybridizationPlant DiseasesApoptosisMammary Neoplasms, ExperimentalDoxycyclineMice, Inbred StrainsSolanum tuberosumMammary Glands, AnimalTranscription, GeneticHyperplasiaDNA-Binding ProteinsChromosomes, Artificial, BacterialNerve Tissue ProteinsGlucuronidaseCloning, MolecularBlotting, NorthernTissue DistributionKeratin-14Gene Expression Regulation, EnzymologicModels, AnimalTime FactorsRecombinant ProteinsEmbryo, MammalianHomeodomain ProteinsUp-RegulationPlant RootsAgrobacteriumAgingRegulatory Sequences, Nucleic AcidGene TargetingOrganisms, Genetically ModifiedMammary Tumor Virus, MousePresenilin-1Lycopersicon esculentumDNAAnimals, Newborntau ProteinsMetallothioneinTransfectionHuntington DiseaseDNA, ComplementaryMice, Inbred C3HCell ProliferationEpidermisSuperoxide DismutaseTrans-ActivatorsSkinCardiomegalyKeratinsCaulimovirusCell Transformation, NeoplasticKidneyDNA, PlantChimeraDroughtsPapillomaRestriction MappingVaccines, EdibleOrgan SizeAmyotrophic Lateral SclerosisPlasmidsGlobinsZebrafish ProteinsIslets of LangerhansNerve DegenerationCarrier ProteinsMuscle, SkeletalGrowth HormoneRNA, PlantGossypiumMaze LearningAgrobacterium tumefaciensMammary Neoplasms, AnimalDown-RegulationChromosomes, Artificial, YeastGlial Fibrillary Acidic ProteinRNA InterferenceStem CellsGene Expression ProfilingGenes, rasDisease ProgressionHomozygoteImmunoblottingTauopathiesSalt-ToleranceGenes, mycBody WeightGene DosageMicroscopy, FluorescenceHeartRepressor ProteinsCell LineageGene SilencingRNAPhosphorylationProto-Oncogene ProteinsBehavior, Animal
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.H-2 Antigens: The major group of transplantation antigens in the mouse.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.Cancer Vaccines: Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.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.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.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.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.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.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.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.Presenilin-1: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.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.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.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.Homozygote: An individual in which both alleles at a given locus are identical.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.Salt-Tolerance: The ability of organisms to sense and adapt to high concentrations of salt in their growth environment.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.

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)

Startseite - Tetracycline Inducible Transgenic Mice - 517629 - Nordwest-GamerStartseite - Tetracycline Inducible Transgenic Mice - 517629 - Nordwest-Gamer
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 ...
Induction of Corneal Epithelial Hypertrophy by FGF-7 in a Binary Inducible Transgenic Mouse Model | IOVS | ARVO JournalsInduction of Corneal Epithelial Hypertrophy by FGF-7 in a Binary Inducible Transgenic Mouse Model | IOVS | ARVO Journals
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 ...
Identification and Characterization of GLP-1 Receptor-Expressing Cells Using a New Transgenic Mouse Model | DiabetesIdentification and Characterization of GLP-1 Receptor-Expressing Cells Using a New Transgenic Mouse Model | Diabetes
Despite wide academic and commercial interest in the actions of GLP-1, attempts to identify the cellular targets of GLP-1 are hampered by the lack of specificity of antibodies to GLP1R. Our development of a new transgenic mouse model expressing Cre recombinase driven by the glp1r promoter provides an antibody-independent method for the identification and characterization of live cells expressing glp1r, using floxed fluorescent reporter strains. The results illuminate not only which tissues exhibited glp1r fluorescence but also those that did not.. Establishing definitively that the GLP1R protein is produced by all glp1r-fluorescent cells will be important, because our use of Cre recombinase results in a permanent activation of the fluorescent reporters, even in cells that no longer express the receptor as well as in the progeny of cells that have once expressed glp1r. Where neurones were identified, we were able to confirm expression of GLP1R protein by demonstrating functional responsiveness to ...
Induction of LacZ Expression in Kera3.2-int-rtTA /tet-O-Cre /Rosa26-LacZ Transgenic Mice | IOVS | ARVO JournalsInduction of LacZ Expression in Kera3.2-int-rtTA /tet-O-Cre /Rosa26-LacZ Transgenic Mice | IOVS | ARVO Journals
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 ...
Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent...Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent...
TY - JOUR. T1 - Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver. AU - Kitteringham, Neil R.. AU - Abdullah, Azman. AU - Walsh, Joanne. AU - Randle, Laura. AU - Jenkins, Rosalind E.. AU - Sison, Rowena. AU - Goldring, Christopher E.P.. AU - Powell, Helen. AU - Sanderson, Christopher. AU - Williams, Samantha. AU - Higgins, Larry. AU - Yamamoto, Masayuki. AU - Hayes, John. AU - Park, B. Kevin. PY - 2010/6/16. Y1 - 2010/6/16. N2 - The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2-/-) are highly susceptible to xenobiotic-mediated toxicity, but the precise molecular basis of enhanced toxicity is unknown. Oligonucleotide array studies suggest that a wide range of gene products is altered constitutively, however no equivalent proteomics analyses have been conducted. To define the range of ...
Chop (Ddit3) is essential for D469del-COMP retention and cell death in chondrocytes in an inducible transgenic mouse model of...Chop (Ddit3) is essential for D469del-COMP retention and cell death in chondrocytes in an inducible transgenic mouse model of...
Am J Pathol. 2012 Feb;180(2):727-37. doi: 10.1016/j.ajpath.2011.10.035. Epub 2011 Dec 7. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Govt
Overexpression of transforming growth factor α in transgenic mice alters nonreproductive, sex-related behavioral differences:...Overexpression of transforming growth factor α in transgenic mice alters nonreproductive, sex-related behavioral differences:...
TY - JOUR. T1 - Overexpression of transforming growth factor α in transgenic mice alters nonreproductive, sex-related behavioral differences. T2 - Interaction with gonadal hormones. AU - Hilakivi-Clarke, L.. PY - 1994. Y1 - 1994. N2 - Sexually dimorphic differences in voluntary sodium intake, locomotor activity, immobility in the swim test, and aggressive behavior were found to be altered in transgenic CD-1 mice that overexpressed transforming growth factor α (TGFα). In contrast to nontransgenic CD-1 mice, immobility in the swim test was longer and sodium intake higher in the male TGFα mice than in the female TGFα mice. These findings indicate that the male TGFα mice exhibited feminization of some behaviors. Furthermore, the male TGFα mice were highly aggressive. Castration reversed the behavioral effects in the adult male transgenic mice, but ovariectomy did not reverse the behavioral effects in the adult female transgenic mice. Thus the feminizing effect of TGFα on some nonreproductive ...
People - Transgenic Mouse/ES Cell Shared Resource - Labnodes - The Vanderbilt Research NetworkPeople - Transgenic Mouse/ES Cell Shared Resource - Labnodes - The Vanderbilt Research Network
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
Vanderbilt Genome Editing Resource - Labnodes - The Vanderbilt Research NetworkVanderbilt Genome Editing Resource - Labnodes - The Vanderbilt Research Network
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...Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in...
Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior.s profile, publications, research topics, and co-authors
Morphological and functional alterations in ventricular myocytes from male transgenic mice with hypertrophic cardiomyopathyMorphological and functional alterations in ventricular myocytes from male transgenic mice with hypertrophic cardiomyopathy
Advanced search is divided into two main parts, and one or more groups in each of the main parts. The main parts are the "Search for" (including) and the "Remove from search" (excluding) part. (The excluding part might not be visible until you hit "NOT" for the first time ...
Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain | JCBActivation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain | JCB
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 ...
Aβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology | EMBO ReportsAβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology | EMBO Reports
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 ...
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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 ...
Immortalization of subpopulations of respiratory epithelial cells from transgenic mice bearing SV40 large T antigen<...Immortalization of subpopulations of respiratory epithelial cells from transgenic mice bearing SV40 large T antigen<...
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 - ...
ALZFORUM | NETWORKING FOR A CUREALZFORUM | NETWORKING FOR A CURE
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.. ...
Recombinant ret oncogene products induce T lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice<...Recombinant ret oncogene products induce T lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice<...
TY - JOUR. T1 - Recombinant ret oncogene products induce T lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice. AU - Yan, D.. AU - Isobe, K. I.. AU - Takahashi, M.. AU - Nakashima, I.. PY - 1994/1/1. Y1 - 1994/1/1. N2 - Recombinant ret oncogene products in complete Freunds adjuvant were injected into normal mice and ret oncogene transgenic mice. Spleen cells from the mice immunized with ret proteins were highly proliferated in vitro by the stimulation of ret proteins. The proliferating T cells have CD4+ phenotype and secreated CTLL-2 reactive interleukins. The peritoneal exudate cells from ret proteinimmunized mice suppressed ret-2 lymphoma, which was derived from ret lymphoma transgenic mice. The peritoneal exudate cells from ret melanoma transgenic mice did not suppress ret-2 lymphoma, when they were immunized with ret proteins.. AB - Recombinant ret oncogene products in complete Freunds adjuvant were injected into normal mice and ret oncogene transgenic mice. ...
Difference between revisions of ANAT2341 Lab 2 - EmbryologyDifference between revisions of "ANAT2341 Lab 2" - Embryology
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 ...
Munin: Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activityMunin: Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity
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 ...
JCI - TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathwaysJCI - TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways
Transgenic mice with cardiac-restricted overexpression of secretable TNF (MHCsTNF) develop progressive LV wall thinning and dilation accompanied by an increase in cardiomyocyte apoptosis and a progressive loss of cytoprotective Bcl-2. To test whether cardiac-restricted overexpression of Bcl-2 would prevent adverse cardiac remodeling, we crossed MHCsTNF mice with transgenic mice harboring cardiac-restricted overexpression of Bcl-2. Sustained TNF signaling resulted in activation of the intrinsic cell death pathway, leading to increased cytosolic levels of cytochrome c, Smac/Diablo and Omi/HtrA2, and activation of caspases -3 and -9. Cardiac-restricted overexpression of Bcl-2 blunted activation of the intrinsic pathway and prevented LV wall thinning; however, Bcl-2 only partially attenuated cardiomyocyte apoptosis. Subsequent studies showed that c-FLIP was degraded, that caspase-8 was activated, and that Bid was cleaved to t-Bid, suggesting that the extrinsic pathway was activated concurrently in ...
Aging | Premature aging and cancer development in transgenic mice lacking functional CYLD - Full TextAging | Premature aging and cancer development in transgenic mice lacking functional CYLD - Full Text
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
Investigation of epithelial canonical and non-canonical NF-κB signaling in lung adenocarcinomaInvestigation of epithelial canonical and non-canonical NF-κB signaling in lung adenocarcinoma
Nuclear factor κ-light chain enhancer of activated B cells (NF-κB) is a transcription factor that can be activated through canonical or non-canonical signaling pathways, and activation of both pathways has been observed in lung adenocarcinoma tumors. However, the mechanistic links between canonical and non-canonical NF-κB signaling and lung tumorigenesis have not been fully elucidated. Using transgenic mouse models, we demonstrate that canonical NF-κB signaling promotes epidermal growth factor receptor (EGFR)-mediated tumor formation through paracrine signaling to the inflammatory microenvironment, with depletion studies identifying macrophages as a critical cell type promoting EGFR-driven lung tumorigenesis. To study non-canonical NF-κB signaling, we developed a novel transgenic mouse model with inducible over-expression of the non-canonical NF-κB component p52 in the airway epithelium. After injection with the lung carcinogen urethane, p52 over-expression led to increased tumor number, ...
Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse...Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse...
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) ...
Increased BMP6 Levels in the Brains of Alzheimers Disease Patients and APP Transgenic Mice Are Accompanied by Impaired...Increased BMP6 Levels in the Brains of Alzheimer's Disease Patients and APP Transgenic Mice Are Accompanied by Impaired...
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 ...
pub H-BRS | Searchpub H-BRS | Search
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 ...
Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain. - PubMed - NCBIEfficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain. - PubMed - NCBI
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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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 ...
Novel cell lines derived from transgenic mice expressing recombinant human proteins | SpringerLinkNovel cell lines derived from transgenic mice expressing recombinant human proteins | SpringerLink
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...
Shirley ShiDu Yan | School of PharmacyShirley ShiDu Yan | School of Pharmacy
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 ...
HACE2 TRANSGENIC MOUSE MODEL FOR CORONAVIRUS (COVID-19) RESEARCH - AnimalabHACE2 TRANSGENIC MOUSE MODEL FOR CORONAVIRUS (COVID-19) RESEARCH - Animalab
In 2007, McCray, Jr. et al from the University of Iowa published a study in which they introduced a vector carrying a human ACE2-coding sequence into wild-type mice and subsequently developed a successful hACE2 transgenic mouse strain. ACE2 expression, which is regulated by the human cytokeratin 18 (K18) promoter in epithelial cells, was observed in the initially infected airway epithelial cells. Studies showed that the K18-hACE2 transgenic mouse infected with a human SARS-CoV strain via intranasal inoculation would not survive. The infection would begin in the airway epithelium, spread to the alveoli and finally out of the lungs to the brain. The infection causes infiltration of macrophages and lymphocytes in the lungs and up-regulation of pro-inflammatory cytokines and chemokines in the lungs and brain. Three to five days following infection, K18-hACE2 mice began to lose weight and become lethargic with labored breathing. All died within seven days. These observations support that transgene ...
Alzheimers Disease Cell Bio - Cell Biology of Disease and ExerciseAlzheimer's Disease Cell Bio - Cell Biology of Disease and Exercise
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 ...
Protocols and Video Articles Authored by Nikolaos SvoronosProtocols and Video Articles Authored by Nikolaos Svoronos
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
Protocols and Video Articles Authored by Tom L. StephenProtocols and Video Articles Authored by Tom L. Stephen
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
Hypertension in Transgenic Mice Expressing the Rac-1 Protein in Vascular Smooth Muscle | HypertensionHypertension in Transgenic Mice Expressing the Rac-1 Protein in Vascular Smooth Muscle | Hypertension
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 ...
Abstract 122: Cardiac mTOR Preserves Cardiac Function Following Ex Vivo Ischemia-Reperfusion in Diet-Induced Obese Mice |...Abstract 122: Cardiac mTOR Preserves Cardiac Function Following Ex Vivo Ischemia-Reperfusion in Diet-Induced Obese Mice |...
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 ...
Control of CD4 effector fate: transforming growth factor beta 1 and interleukin 2 synergize to prevent apoptosis and promote...Control of CD4 effector fate: transforming growth factor beta 1 and interleukin 2 synergize to prevent apoptosis and promote...
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. | Open-iAbsence of lung fibrosis in TGFβ1 overexpressing mice. | Open-i
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
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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 ...
KAKEN - Research Projects | Production of monoclonal antibody specific to HLA by utilizing HLA transgenic mice. (KAKENHI...KAKEN - Research Projects | Production of monoclonal antibody specific to HLA by utilizing HLA transgenic mice. (KAKENHI...
Principal Investigator：NISHIMURA Yasuharu, Project Period (FY)：1989 - 1991, Research Category：Grant-in-Aid for Developmental Scientific Research., Research Field：Immunology
Evaluating Passive Immunotherapy using Aged Transgenic Animals of Tauopathy</em>...Evaluating Passive Immunotherapy using Aged Transgenic Animals of Tauopathy</em>...
TY - CONF. T1 - Evaluating Passive Immunotherapy using Aged Transgenic Animals of Tauopathy. AU - Al Lahham, Rabab. AU - Bittar, Alice. AU - Montalbano, Mauro. AU - Carretero Murillo, Mariana. AU - McAllen, Salome. AU - Bhatt, Nemil. AU - Ellsworth, Anna. AU - Kayed, Rakez. PY - 2018/4. Y1 - 2018/4. M3 - Poster. ER - ...
ResearchResearch
Our lab is focused on understanding the signals for proper development and function of CD4 T cell memory. We have generated two CD4 T cell receptor transgenic mice specific for the same naturally occurring epitope from Listeria monocytogenes. These transgenic mice, called LLO118 and LLO56, have dramatically different primary and secondary responses to infection. LLO118 has a strong primary response relative to LLO56, whereas LLO56 has a much better memory response compared to LLO118. Understanding why these dramatic differences between primary and secondary responses exist could provide important insights into why some T cells are better at providing immunity to infection and generating memory cells and how this can be improved ...
T cell tolerance and activation to a transgene-encoded tumor antigen - Antoniou - 1996 - European Journal of Immunology - Wiley...T cell tolerance and activation to a transgene-encoded tumor antigen - Antoniou - 1996 - European Journal of Immunology - Wiley...
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 ...
B cells solicit their own help from T cells. | Journal of Experimental Medicine | Rockefeller University PressB cells solicit their own help from T cells. | Journal of Experimental Medicine | Rockefeller University Press
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. ...
CSHLPress.com - HNF6 Rev-erb-alphaCSHLPress.com - HNF6 Rev-erb-alpha
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 ...
Multiple Sclerosis Research: Mouse model of a Virus Infection doesnt get MSMultiple Sclerosis Research: Mouse model of a Virus Infection doesn't get MS
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 ...
Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus | GutHedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus | Gut
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.. ...
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Spontaneous Organ-Specific Th2-Mediated Autoimmunity in TCR Transgenic Mice | The Journal of ImmunologySpontaneous Organ-Specific Th2-Mediated Autoimmunity in TCR Transgenic Mice | The Journal of Immunology
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 ...
Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice<...Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice<...
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 ...
Increased expression of keratin 16 causes anomalies in cytoarchitecture and keratinization in transgenic mouse skin. | JCBIncreased expression of keratin 16 causes anomalies in cytoarchitecture and keratinization in transgenic mouse skin. | JCB
Injury to epidermis and other stratified epithelia triggers profound but transient changes in the pattern of keratin expression. In postmitotic cells located at the wound edge, a strong induction of K6, K16, and K17 synthesis occurs at the expense of the keratins produced under the normal situation. The functional significance of these alterations in keratin expression is not known. Here, we report that overexpression of a wild-type human K16 gene in a tissue-specific fashion in transgenic mice causes aberrant keratinization of the hair follicle outer root sheath and proximal epidermis, and it leads to hyperproliferation and increased thickness of the living layers (acanthosis), as well as cornified layers (hyperkeratosis). The pathogenesis of lesions in transgenic mouse skin begins with a reorganization of keratin filaments in postmitotic keratinocytes, and it progresses in a transgene level-dependent fashion to include disruption of keratinocyte cytoarchitecture and structural alterations in ...
Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice...Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice...
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% ...
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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 ...
Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal...Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal...
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 ...
Association of Aortic Atherosclerosis with Cerebral β-Amyloidosis and Learning Deficits in a Mouse Model of Alzheimers DiseaseAssociation of Aortic Atherosclerosis with Cerebral β-Amyloidosis and Learning Deficits in a Mouse Model of Alzheimer's Disease
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 ...
HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases<...HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases<...
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 ...
Expression of a human O6-alkylguanine-DNA-alkyltransferase cDNA in human cells and transgenic mice.Expression of a human O6-alkylguanine-DNA-alkyltransferase cDNA in human cells and transgenic mice.
A truncated human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA was ligated into an expression vector under the control of the mouse metallothionein-1 gene promotor and upstream of part of the human growth hormone gene to provide splice and polyadenylation signals. Transfection of this construct into human cells resulted in very high levels of ATase expression (more than 300 fmoles/mg protein versus less than 2 fm/mg protein in parent vector transfected control cells). Microinjection of a 4.2 kb fragment of this vector into B6D2F2 mouse embryos and implantation of survivors into pseudopregnant females has so far generated 35 offspring. Southern analysis of tail tip DNA has shown that 11 of the offspring are transgenic for the human ATase gene, between 1 and at least 30 copies of the gene being detected. Human ATase transcripts were detected in total RNA extracted from liver obtained from two male transgenic mice by partial hepatectomy. Cell free extracts of liver samples from five transgenic ...
Abstract 3771: Blocking of Transforming Growth Factor (TGF)-β Signaling Exacerbates Pressure Overload-induced Left Ventricular...Abstract 3771: Blocking of Transforming Growth Factor (TGF)-β Signaling Exacerbates Pressure Overload-induced Left Ventricular...
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 ...
Leukaemogenesis by the ΔMo + SV Moloney murine leukaemia virus (M-MuLV) variant in Eµ pim-1 transgenic mice: high frequency of...Leukaemogenesis by the ΔMo + SV Moloney murine leukaemia virus (M-MuLV) variant in Eµ pim-1 transgenic mice: high frequency of...
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
Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo. - The Kennedy...Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo. - The Kennedy...
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
Transgenic mice expressing the human inducible Hsp70 have hippocampal neurons resistant to ischemic injury. - Plumier Jean...Transgenic mice expressing the human inducible Hsp70 have hippocampal neurons resistant to ischemic injury. - Plumier Jean...
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 ...
009 Endothelial-specific overexpression of Nox2 enhances angiotensin II-induced cardiac dysfunction and fibrosis | Heart009 Endothelial-specific overexpression of Nox2 enhances angiotensin II-induced cardiac dysfunction and fibrosis | Heart
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 ...
Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice | Journal of Cell...Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice | Journal of Cell...
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 ...
OpenEmory | Search ResultsOpenEmory | Search Results
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 ...
Apoptosis Is Not Increased in Myocardium Overexpressing Type 2 Angiotensin II Receptor in Transgenic Mice | HypertensionApoptosis Is Not Increased in Myocardium Overexpressing Type 2 Angiotensin II Receptor in Transgenic Mice | Hypertension
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 ...
Impaired proliferation and survival of activated B cells in transgenic mice that express a dominant-negative cAMP-response...Impaired proliferation and survival of activated B cells in transgenic mice that express a dominant-negative cAMP-response...
The cAMP-response element-binding protein (CREB) is activated by phosphorylation on serine 133 and mediates the proliferative response to a number of different signals. A mutant CREB with a serine to alanine substitution at position 133 (CREBM1) functions as a dominant-negative inhibitor. Transgenic mice that express the dominant-negative CREB protein in B lymphocytes were developed as a means to study the effects of the inhibition of CREB function on B-cell proliferation and survival. We have shown previously that CREB up-regulates Bcl-2 expression in B cells in response to activation signals. B cells from CREBM1 transgenic mice expressed lower levels of Bcl-2 with and without stimulation. Proliferation of B cells from the transgenic mice was impaired in part by lack of induction of activator protein 1 (AP1) transcription factors. B cells from the transgenic mice were more susceptible to induction of apoptosis with several different agents, consistent with the decreased expression of Bcl-2. ...
Abstract P273: Enhancement of Proteasomal Function Protects Against Proteinopathy and Myocardial Ischemia-Reperfusion Injury in...Abstract P273: Enhancement of Proteasomal Function Protects Against Proteinopathy and Myocardial Ischemia-Reperfusion Injury in...
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 ...
B-Myb Represses Vascular Smooth Muscle Cell Collagen Gene Expression and Inhibits Neointima Formation After Arterial Injury |...B-Myb Represses Vascular Smooth Muscle Cell Collagen Gene Expression and Inhibits Neointima Formation After Arterial Injury |...
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 ...
Doi:10.1016/j.jalz.2009.05.027Doi:10.1016/j.jalz.2009.05.027
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 ...
Dlx5/6-Enhancer Directed Expression of Cre Recombinase in the Pharyngeal Arches and Brain<...Dlx5/6-Enhancer Directed Expression of Cre Recombinase in the Pharyngeal Arches and Brain<...
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 ...
Enhanced susceptibility to lipopolysaccharide-induced arthritis and endotoxin shock in interleukin-32 alpha transgenic mice...Enhanced susceptibility to lipopolysaccharide-induced arthritis and endotoxin shock in interleukin-32 alpha transgenic mice...
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
Generation of a mouse line harboring a Bi-transgene expressing luciferase and tamoxifen-activatable creER(T2) recombinase in...Generation of a mouse line harboring a Bi-transgene expressing luciferase and tamoxifen-activatable creER(T2) recombinase in...
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
Two Distinct Populations of CD4 T Cells Play Different Roles in Immune System | Dartmouth-HitchcockTwo Distinct Populations of CD4 T Cells Play Different Roles in Immune System | Dartmouth-Hitchcock
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 ...
JCI Insight - Functional significance of the discordance between transcriptional profile and left ventricular structure...JCI Insight - Functional significance of the discordance between transcriptional profile and left ventricular structure...
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 ...
Abstract 12920: Interaction Between Coupling Factor 6 and Ecto-F1FO Complex Induces Hypertension and Diabetes by Tissue...Abstract 12920: Interaction Between Coupling Factor 6 and Ecto-F1FO Complex Induces Hypertension and Diabetes by Tissue...
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 ...
Plus itPlus it
Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc complementary DNA and mouse metallothionein 1 promoter-human transforming growth factor α complementary DNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and transforming growth factor α as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction ...
PoliovirusPoliovirus
Lee-Boot effectLee-Boot effect
TGF alphaTGF alpha
Swedish mutationSwedish mutation
Janet SawickiJanet Sawicki
Interleukin 10Interleukin 10
Monoclonal antibodyMonoclonal antibody
EtanerceptEtanercept
Vincent RacanielloVincent Racaniello
Polio vaccinePolio vaccine
RegeneronRegeneron
Thymic nurse cellThymic nurse cell
AlirocumabAlirocumab
Agouti-related peptideAgouti-related peptide
GNLYGNLY
ABCA1ABCA1
Jacqueline CrawleyJacqueline Crawley
Green fluorescent proteinGreen fluorescent protein
Elmezzi Graduate School of Molecular MedicineElmezzi Graduate School of Molecular Medicine
Programmed cell deathProgrammed cell death
Alzheimers diseaseAlzheimer's disease
Alpha-taxilinAlpha-taxilin
ADAM12ADAM12
Mating plugMating plug
PRNDPRND
Cre-Lox recombinationCre-Lox recombination
NELL1NELL1
HIV associated cardiomyopathyHIV associated cardiomyopathy
S100BS100B
SHIRPASHIRPA
ZygosityZygosity
Genetically modified tomatoGenetically modified tomato
ഗ്രെഗ് എൽ. സെമെൻസ - വിക്കിപീഡിയഗ്രെഗ് എൽ. സെമെൻസ - വിക്കിപീഡിയ
PSEN1PSEN1
PicornavirusPicornavirus
CD2, a enciclopedia libreCD2, a enciclopedia libre
JC virusJC virus
ICI-118,551ICI-118,551
Acute inhalation injuryAcute inhalation injury
RetrovirusRetrovirus
List of atheists in science and technologyList of atheists in science and technology
Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Beta-amiloide, a enciclopedia libreBeta-amiloide, a enciclopedia libre
AutophagyAutophagy
Rekayasa genetika bahasa Indonesia, ensiklopedia bebasRekayasa genetika bahasa Indonesia, ensiklopedia bebas
AutophagyAutophagy
Epigenetics of neurodegenerative diseasesEpigenetics of neurodegenerative diseases
PRNPPRNP
Calorie restrictionCalorie restriction
GlycosylationGlycosylation
Eric KandelEric Kandel
Interleukin 15Interleukin 15
Regulation of genetic engineeringRegulation of genetic engineering
Arachidonate 5-lipoxygenaseArachidonate 5-lipoxygenase
Parkinsons diseaseParkinson's disease
Sea cucumberSea cucumber
LipomLipom
ಹಂಟಿಂಗ್ಟನ್‌‌ನ ಕಾಯಿಲೆ - ವಿಕಿಪೀಡಿಯಹಂಟಿಂಗ್ಟನ್‌‌ನ ಕಾಯಿಲೆ - ವಿಕಿಪೀಡಿಯ
AntioxidantAntioxidant
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsTechnology, Industry, AgricultureInformation ScienceHealth Care
Mice, TransgenicMice, Inbred C57BLTransgenesDisease Models, AnimalPlants, Genetically ModifiedGene ExpressionRats, TransgenicPromoter Regions, GeneticAnimals, Genetically ModifiedCrosses, GeneticMolecular Sequence DataThymus GlandMice, Inbred CBAReceptors, Antigen, T-Cell, alpha-betaH-2 AntigensImmunohistochemistryT-LymphocytesRNA, MessengerBase SequenceClonal DeletionMice, KnockoutB-LymphocytesSpleenMice, Inbred DBAReceptors, Antigen, T-CellEpitopes, T-LymphocyteImmune ToleranceAntigens, Polyomavirus TransformingGreen Fluorescent ProteinsCD4-Positive T-LymphocytesLymphocyte ActivationMice, Inbred BALB CPhenotypePapillomavirus E7 ProteinsImmunizationGene Expression RegulationCell DifferentiationBrainCells, CulturedHybridomasMutationImmunoglobulin kappa-ChainsPeptide FragmentsFlow CytometryAmino Acid SequenceDNA PrimersAutoantigensCancer VaccinesT-Lymphocytes, CytotoxicT-Lymphocyte SubsetsAntigens, CD4Reverse Transcriptase Polymerase Chain ReactionLiverCell DivisionMembrane ProteinsImmunoglobulin GNeuronsMembrane GlycoproteinsCell LineAutoantibodiesAntigens, CDTobaccoPolymerase Chain ReactionCD8-Positive T-LymphocytesSignal TransductionInterferon-gammaCytotoxicity, ImmunologicNuclear ProteinsCytokinesInterleukin-4PeptidesAntibodies, MonoclonalPlants, ToxicTumor Cells, CulturedGene Expression Regulation, PlantOrgan SpecificityPlant ProteinsGenes, ReporterGene Expression Regulation, DevelopmentalRecombinant Fusion ProteinsArabidopsisAmyloid beta-Protein PrecursorLuminescent ProteinsPlant LeavesTransformation, GeneticIntegrasesGenetic EngineeringTranscription FactorsAlzheimer DiseaseLac OperonPlaque, AmyloidAmyloid beta-PeptidesOryza sativaGenetic VectorsBlotting, WesternZebrafishGenes, PlantEnhancer Elements, GeneticBlotting, Southernbeta-GalactosidaseSeedsArabidopsis ProteinsGene Transfer TechniquesMyocardiumIn Situ HybridizationPlant DiseasesApoptosisMammary Neoplasms, ExperimentalDoxycyclineMice, Inbred StrainsSolanum tuberosumMammary Glands, AnimalTranscription, GeneticHyperplasiaDNA-Binding ProteinsChromosomes, Artificial, BacterialNerve Tissue ProteinsGlucuronidaseCloning, MolecularBlotting, NorthernTissue DistributionKeratin-14Gene Expression Regulation, EnzymologicModels, AnimalTime FactorsRecombinant ProteinsEmbryo, MammalianHomeodomain ProteinsUp-RegulationPlant RootsAgrobacteriumAgingRegulatory Sequences, Nucleic AcidGene TargetingOrganisms, Genetically ModifiedMammary Tumor Virus, MousePresenilin-1Lycopersicon esculentumDNAAnimals, Newborntau ProteinsMetallothioneinTransfectionHuntington DiseaseDNA, ComplementaryMice, Inbred C3HCell ProliferationEpidermisSuperoxide DismutaseTrans-ActivatorsSkinCardiomegalyKeratinsCaulimovirusCell Transformation, NeoplasticKidneyDNA, PlantChimeraDroughtsPapillomaRestriction MappingVaccines, EdibleOrgan SizeAmyotrophic Lateral SclerosisPlasmidsGlobinsZebrafish ProteinsIslets of LangerhansNerve DegenerationCarrier ProteinsMuscle, SkeletalGrowth HormoneRNA, PlantGossypiumMaze LearningAgrobacterium tumefaciensMammary Neoplasms, AnimalDown-RegulationChromosomes, Artificial, YeastGlial Fibrillary Acidic ProteinRNA InterferenceStem CellsGene Expression ProfilingGenes, rasDisease ProgressionHomozygoteImmunoblottingTauopathiesSalt-ToleranceGenes, mycBody WeightGene DosageMicroscopy, FluorescenceHeartRepressor ProteinsCell LineageGene SilencingRNAPhosphorylationProto-Oncogene ProteinsBehavior, Animal
Transgenic mice | DevelopmentTransgenic mice | Development
Spontaneous Organ-Specific Th2-Mediated Autoimmunity in TCR Transgenic Mice | The Journal of ImmunologySpontaneous Organ-Specific Th2-Mediated Autoimmunity in TCR Transgenic Mice | The Journal of Immunology
Hypertension in Transgenic Mice Expressing the Rac-1 Protein in Vascular Smooth Muscle | HypertensionHypertension in Transgenic Mice Expressing the Rac-1 Protein in Vascular Smooth Muscle | Hypertension
Transgenic Mice Advice?Transgenic Mice Advice?
Transgenic Mice Advice?Transgenic Mice Advice?
Heart and bone tumors in transgenic mice | PNASHeart and bone tumors in transgenic mice | PNAS
Transgenic mouse models of Alzheimers disease. - PubMed - NCBITransgenic mouse models of Alzheimer's disease. - PubMed - NCBI
Spontaneous generation of anchorless prions in transgenic mice | PNASSpontaneous generation of anchorless prions in transgenic mice | PNAS
NASA - Muscle Atrophy of Muscle Sparing in Transgenic MiceNASA - Muscle Atrophy of Muscle Sparing in Transgenic Mice
Thymic lymphomas in interleukin 9 transgenic mice. - PubMed - NCBIThymic lymphomas in interleukin 9 transgenic mice. - PubMed - NCBI
JCI - Transgenic rescue of insulin receptor-deficient miceJCI - Transgenic rescue of insulin receptor-deficient mice
Application of Echocardiography on Transgenic Mice with CardiomyopathiesApplication of Echocardiography on Transgenic Mice with Cardiomyopathies
Alb-uPA Transgenic Mice - The Digitized Atlas of Mouse Liver LesionsAlb-uPA Transgenic Mice - The Digitized Atlas of Mouse Liver Lesions
A transgenic mouse assay for agouti protein activity. | GeneticsA transgenic mouse assay for agouti protein activity. | Genetics
Introducing Human APOE into Aβ Transgenic Mouse ModelsIntroducing Human APOE into Aβ Transgenic Mouse Models
Recent Articles | Transgenic Mice | The Scientist Magazine®Recent Articles | Transgenic Mice | The Scientist Magazine®
A transgenic insertion causing cryptorchidism in miceA transgenic insertion causing cryptorchidism in mice
JCI - Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl.JCI - Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl.
Atherosclerosis in APOE*3-Leiden Transgenic Mice | CirculationAtherosclerosis in APOE*3-Leiden Transgenic Mice | Circulation
The AICD Test? Transgenic Mice Show Neurodegeneration | ALZFORUMThe AICD Test? Transgenic Mice Show Neurodegeneration | ALZFORUM
Transgenic mouse models of neurodegenerative disease: Opportunities for therapeutic development | SpringerLinkTransgenic mouse models of neurodegenerative disease: Opportunities for therapeutic development | SpringerLink
Case Study: Polycystic Livers in a Transgenic Mouse Line: Ingenta ConnectCase Study: Polycystic Livers in a Transgenic Mouse Line: Ingenta Connect
Mice Transgenic for Human Angiotensin-converting Enzyme 2 Provide...: Ingenta ConnectMice Transgenic for Human Angiotensin-converting Enzyme 2 Provide...: Ingenta Connect
Acute Leukaemia in bcr/abl Transgenic MiceAcute Leukaemia in bcr/abl Transgenic Mice
Transgenic Mouse Technology: Principles and Methods | SpringerLinkTransgenic Mouse Technology: Principles and Methods | SpringerLink
Definition of transgenic mice - NCI Dictionary of Cancer Terms - National Cancer InstituteDefinition of transgenic mice - NCI Dictionary of Cancer Terms - National Cancer Institute
Conditional Ablation of Cerebellar Astrocytes in Postnatal Transgenic Mice | Journal of NeuroscienceConditional Ablation of Cerebellar Astrocytes in Postnatal Transgenic Mice | Journal of Neuroscience
NF-κB Promotes Muscle Wasting in Transgenic Mice | Science SignalingNF-κB Promotes Muscle Wasting in Transgenic Mice | Science Signaling
Recent Articles | Transgenic Mice And Disease/Medicine | The Scientist Magazine®Recent Articles | Transgenic Mice And Disease/Medicine | The Scientist Magazine®
Transgenic Mice Accumulate Human Tau in Degenerating Hippocampal Neurons | ALZFORUMTransgenic Mice Accumulate Human Tau in Degenerating Hippocampal Neurons | ALZFORUM
Impairment of Collateral Formation in Lipoprotein(a) Transgenic Mice | CirculationImpairment of Collateral Formation in Lipoprotein(a) Transgenic Mice | Circulation
Patent US6372957 - Transgenic mouse comprising a MEF2 binding site operatively linked to an ... - Google PatentsPatent US6372957 - Transgenic mouse comprising a MEF2 binding site operatively linked to an ... - Google Patents
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsTechnology, Industry, AgricultureInformation ScienceHealth Care
Mice, TransgenicMice, Inbred C57BLTransgenesDisease Models, AnimalPlants, Genetically ModifiedGene ExpressionRats, TransgenicPromoter Regions, GeneticAnimals, Genetically ModifiedCrosses, GeneticMolecular Sequence DataThymus GlandMice, Inbred CBAReceptors, Antigen, T-Cell, alpha-betaH-2 AntigensImmunohistochemistryT-LymphocytesRNA, MessengerBase SequenceClonal DeletionMice, KnockoutB-LymphocytesSpleenMice, Inbred DBAReceptors, Antigen, T-CellEpitopes, T-LymphocyteImmune ToleranceAntigens, Polyomavirus TransformingGreen Fluorescent ProteinsCD4-Positive T-LymphocytesLymphocyte ActivationMice, Inbred BALB CPhenotypePapillomavirus E7 ProteinsImmunizationGene Expression RegulationCell DifferentiationBrainCells, CulturedHybridomasMutationImmunoglobulin kappa-ChainsPeptide FragmentsFlow CytometryAmino Acid SequenceDNA PrimersAutoantigensCancer VaccinesT-Lymphocytes, CytotoxicT-Lymphocyte SubsetsAntigens, CD4Reverse Transcriptase Polymerase Chain ReactionLiverCell DivisionMembrane ProteinsImmunoglobulin GNeuronsMembrane GlycoproteinsCell LineAutoantibodiesAntigens, CDTobaccoPolymerase Chain ReactionCD8-Positive T-LymphocytesSignal TransductionInterferon-gammaCytotoxicity, ImmunologicNuclear ProteinsCytokinesInterleukin-4PeptidesAntibodies, MonoclonalPlants, ToxicTumor Cells, CulturedGene Expression Regulation, PlantOrgan SpecificityPlant ProteinsGenes, ReporterGene Expression Regulation, DevelopmentalRecombinant Fusion ProteinsArabidopsisAmyloid beta-Protein PrecursorLuminescent ProteinsPlant LeavesTransformation, GeneticIntegrasesGenetic EngineeringTranscription FactorsAlzheimer DiseaseLac OperonPlaque, AmyloidAmyloid beta-PeptidesOryza sativaGenetic VectorsBlotting, WesternZebrafishGenes, PlantEnhancer Elements, GeneticBlotting, Southernbeta-GalactosidaseSeedsArabidopsis ProteinsGene Transfer TechniquesMyocardiumIn Situ HybridizationPlant DiseasesApoptosisMammary Neoplasms, ExperimentalDoxycyclineMice, Inbred StrainsSolanum tuberosumMammary Glands, AnimalTranscription, GeneticHyperplasiaDNA-Binding ProteinsChromosomes, Artificial, BacterialNerve Tissue ProteinsGlucuronidaseCloning, MolecularBlotting, NorthernTissue DistributionKeratin-14Gene Expression Regulation, EnzymologicModels, AnimalTime FactorsRecombinant ProteinsEmbryo, MammalianHomeodomain ProteinsUp-RegulationPlant RootsAgrobacteriumAgingRegulatory Sequences, Nucleic AcidGene TargetingOrganisms, Genetically ModifiedMammary Tumor Virus, MousePresenilin-1Lycopersicon esculentumDNAAnimals, Newborntau ProteinsMetallothioneinTransfectionHuntington DiseaseDNA, ComplementaryMice, Inbred C3HCell ProliferationEpidermisSuperoxide DismutaseTrans-ActivatorsSkinCardiomegalyKeratinsCaulimovirusCell Transformation, NeoplasticKidneyDNA, PlantChimeraDroughtsPapillomaRestriction MappingVaccines, EdibleOrgan SizeAmyotrophic Lateral SclerosisPlasmidsGlobinsZebrafish ProteinsIslets of LangerhansNerve DegenerationCarrier ProteinsMuscle, SkeletalGrowth HormoneRNA, PlantGossypiumMaze LearningAgrobacterium tumefaciensMammary Neoplasms, AnimalDown-RegulationChromosomes, Artificial, YeastGlial Fibrillary Acidic ProteinRNA InterferenceStem CellsGene Expression ProfilingGenes, rasDisease ProgressionHomozygoteImmunoblottingTauopathiesSalt-ToleranceGenes, mycBody WeightGene DosageMicroscopy, FluorescenceHeartRepressor ProteinsCell LineageGene SilencingRNAPhosphorylationProto-Oncogene ProteinsBehavior, Animal
TransgeneVivoVitroTumorNormal miceStrainsEmbryosExhibitCONCLUSIONSModelEmbryoProteinMicroinjectionCellsPlasmidPhenotypeTumorC57BlPromoterWild-type miceGained from transgenic mouse modelsFluorescentModel of Alzheimer's diseaseSingle transgenic miceAlzheimer's DiseaseJournal of NeuroscieMolecularLine of transgenicInduced plurGenetically engineeredGenomeMutantGeneticsMutationOncogeneOverexpressLittermatesDiseaseReporterHuman apolipoproteinMimicLocusLesionsChimericEmbryosMutagenesisInvestigatorsNeuronSimian viHumansBehavioralLungs and brainPostnatalPeptide
Transgene1
Vivo2
Vitro1
  • Spleen cells from the mice immunized with ret proteins were highly proliferated in vitro by the stimulation of ret proteins. (fujita-hu.ac.jp)
Tumor3
Normal mice1
Strains1
Embryos5
Exhibit1
CONCLUSIONS1
  • Conclusions Our results revealed anxiety-related traits and locomotor differences between transgenic mice expressing constitutive active MAPKAPK5 and control littermates. (uit.no)
Model2
  • Among these mouse models, Lemonnier laboratory has created the new generation of humanized HLA-transgenic mice like the HLA-A*0201/DRB1*0101 (A2/DR1) mouse model. (oncotarget.com)
  • 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. (uit.no)
Embryo1
Protein1
Microinjection1
Cells2
Plasmid4
Phenotype14
Tumor10
C57Bl8
Promoter14
Wild-type mice11
Gained from transgenic mouse models1
Fluorescent9
Model of Alzheimer's disease1
Single transgenic mice2
Alzheimer's Disease4
Journal of Neuroscie2
  • Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid β peptides but not on plaque formation," Journal of Neuroscience , vol. 22, no. 24, pp. 10539-10548, 2002. (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)
Molecular6
Line of transgenic1
Induced plur1
  • Reprogramming cells within live mice yields a new type of induced pluripotent stem cell. (the-scientist.com)
Genetically engineered4
Genome6
  • Capecchi, M.R. (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. (springer.com)
  • 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)
  • To elucidate pathological roles of the virus in disease, transgenic mice were produced that carry the HTLV-I genome. (sciencemag.org)
  • 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)
  • The first involves pronuclear injection into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. (wikipedia.org)
Mutant2
Genetics1
  • Introduction of foreign DNA into the mouse germ line is considered a major technical advancement in the fields of developmental biology and genetics. (springer.com)
Mutation4
Oncogene1
  • In an attempt to determine the susceptibility of haploid, round spermatids to neoplastic transformation by this oncogene, transgenic mice were generated that harbored a chimeric gene composed of the SV40 T-antigen genes fused to the 5' and 3' flanking sequences of the mouse protamine 1 gene. (pnas.org)
Overexpress2
Littermates7
Disease20
  • 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)
  • Bradley, A, van der Weyden, L. (2006) Mouse: Chromosome Engineering for Modeling Human Disease. (springer.com)
  • In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. (ahajournals.org)
  • A team at the Spanish National Cancer Research Centre (CNIO) led by Mar-a Blasco has successfully created a transgenic mouse model that simulates the disease in humans. (news-medical.net)
  • A transgenic mouse developed at Cincinnati Children's to model the deadly childhood immune disease HLH (hemophagocytic lymphohistiocytosis) may play a key role in saving lives during the COVID-19 virus pandemic. (news-medical.net)
  • He also noticed that severe COVID-19 disease clinical manifestations are very similar to those seen in transgenic laboratory mice created to faithfully mimic human secondary HLH in the lab. (news-medical.net)
  • 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)
  • While minor differences in weight fluctuation were noted between male and female mice after infection, the study did not indicate that gender played a major role in SARS-CoV-2 infectivity or disease progression. (newswise.com)
  • This study is the first to identify the amount of virus necessary during an initial exposure for the transgenic mice to develop severe COVID-19 disease. (newswise.com)
  • In addition to establishing the K18 hACE2 transgenic mouse model supplied by The Jackson Laboratory, researchers also found these transgenic mice were the most susceptible to severe COVID-19 disease progression and produced what is known as a chemokine storm. (newswise.com)
  • 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)
  • 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)
  • 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)
  • 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)
Reporter3
Human apolipoprotein2
  • 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)
Mimic1
Locus3
  • 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)
Lesions5
  • 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)
  • This paper presents the first comprehensive histopathological characterization of transgenic PyV-mT hyperplasias together with classical transplantation experiments designed to test the growth potential of these lesions. (aacrjournals.org)
  • The PG-1 transgenic mice had significantly lower bacterial loads in their lungs and reduced numbers of pulmonary pathological lesions. (scialert.net)
Chimeric5
Embryos1
  • 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)
Mutagenesis1
Investigators3
Neuron3
  • In the developing mouse hippocampus, intrinsic neuronal excitability does not alter CA3 neuron development but regulates spine formation and synaptic transmission in CA1 neurons. (biologists.org)
  • These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. (broadinstitute.org)
  • In the present short paper, we summarize the current achievements of modeling neuron loss in transgenic mice based on APP/A β overexpression. (pubmedcentralcanada.ca)
Simian vi1
  • To determine whether the enhancement is a general outcome of splicing or is dependent on the particular intron, we also produced equivalent transgenics carrying the widely used simian virus 40 small-t intron. (asm.org)
Humans4
  • Previous attempts to culture PGCs from mice and humans produced embryonic germ cells that look and act like embryonic stem cells. (rxpgnews.com)
  • In this study, scientists showed the K18 hACE2 transgenic mice not only succumbed to the infection but showed systemic (multiple organ) infection with significant virus detected in the nasal passages, lungs, and brain - all organs greatly impacted by SARS-CoV-2 in humans. (newswise.com)
  • 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)
Behavioral5
  • Takashima's team also reports weakened neural activity in the hippocampi of their transgenic mice, which they attribute to a smaller number of functional neurons, as well as impaired performance in two rodent behavioral tests. (alzforum.org)
  • how do I run behavioral assays to find out what's wrong with my mouse? (wiley.com)
  • to discover the wealth of mouse behavioral tasks and to get the guidance you need to select the best methods and necessary controls. (wiley.com)
  • Neurodevelopment and Neurodegeneration" discusses mouse behavioral tasks relevant to neurodevelopmental diseases, such as mental retardation and autism, and to neurodegenerative diseases, such as Alzheimers, Parkinsons, Huntingtons, and amyotrophic lateral sclerosis. (wiley.com)
  • Behavioral Phenotyping of Transgenic and Knockout Mice, Second Edition has been written in Dr. Crawley's private capacity, outside of her professional position at the National Institutes of Health. (wiley.com)
Lungs and brain1
  • The team at Texas Biomed, led by Dr. Luis Martínez-Sobrido, Dr. Jordi B. Torrelles and Dr. Joanne Turner, showed detection of virus in the nasal passages, lungs and brain of the K18 hACE2 transgenic mice. (newswise.com)
Postnatal4
  • 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)
Peptide1
  • Impaired fertility in transgenic mice overexpressing Betacellulin Peptide growth factors regulate many cellular functions by autocrine, paracrine, juxtacrine or endocrine mechanisms. (uni-muenchen.de)
Transgenic mice | Development
Transgenic mice | Development (dev.biologists.org)
Ataxin-2 Regulates RGS8 Translation in a New BAC-SCA2 Transgenic Mouse Model
Ataxin-2 Regulates RGS8 Translation in a New BAC-SCA2 Transgenic Mouse Model (journals.plos.org)
Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions
Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions (journals.plos.org)
Resveratrol Inhibits Pancreatic Cancer Stem Cell Characteristics in Human and KrasG12D Transgenic Mice by Inhibiting...
Resveratrol Inhibits Pancreatic Cancer Stem Cell Characteristics in Human and KrasG12D Transgenic Mice by Inhibiting... (journals.plos.org)
Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins | Nature Communications
Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins | Nature Communications (nature.com)
Search Results
Search Results (springer.com)
Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels | PNAS
Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels | PNAS (pnas.org)
Poliovirus - Wikipedia
Poliovirus - Wikipedia (en.wikipedia.org)
Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease | PNAS
Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease | PNAS (pnas.org)
P63 induces key target genes required for epidermal morphogenesis | PNAS
P63 induces key target genes required for epidermal morphogenesis | PNAS (pnas.org)
Non-invasive monitoring of alternative splicing outcomes to identify candidate therapies for myotonic dystrophy type 1 | Nature...
Non-invasive monitoring of alternative splicing outcomes to identify candidate therapies for myotonic dystrophy type 1 | Nature... (nature.com)
Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis | PNAS
Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis | PNAS (pnas.org)
Essential role of retinoblastoma protein in mammalian hair cell development and hearing | PNAS
Essential role of retinoblastoma protein in mammalian hair cell development and hearing | PNAS (pnas.org)
Tumor Models in Cancer Research | SpringerLink
Tumor Models in Cancer Research | SpringerLink (link.springer.com)
Plus it
Plus it (jneurosci.org)
Frontiers | Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders? | Microbiology
Frontiers | Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders? | Microbiology (frontiersin.org)
Frontiers | The Importance of Aquaporin 1 in Pancreatitis and Its Relation to the CFTR Cl- Channel | Physiology
Frontiers | The Importance of Aquaporin 1 in Pancreatitis and Its Relation to the CFTR Cl- Channel | Physiology (frontiersin.org)
Frontiers | Dysregulation of Astrocytic HMGB1 Signaling in Amyotrophic Lateral Sclerosis | Neuroscience
Frontiers | Dysregulation of Astrocytic HMGB1 Signaling in Amyotrophic Lateral Sclerosis | Neuroscience (frontiersin.org)
Heart and bone tumors in transgenic mice | PNAS
Heart and bone tumors in transgenic mice | PNAS (pnas.org)
Brainbow: New Resources and Emerging Biological Applications for Multicolor Genetic Labeling and Analysis | Genetics
Brainbow: New Resources and Emerging Biological Applications for Multicolor Genetic Labeling and Analysis | Genetics (genetics.org)
Motor Nerve Arborization Requires Proteolytic Domain of Damage-Induced Neuronal Endopeptidase (DINE) during Development |...
Motor Nerve Arborization Requires Proteolytic Domain of Damage-Induced Neuronal Endopeptidase (DINE) during Development |... (jneurosci.org)
Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via...
Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via... (diabetes.diabetesjournals.org)