Animals, Congenic: Animals that are produced through selective breeding to eliminate genetic background differences except for a single or few specific loci. They are used to investigate the contribution of genetic background differences to PHENOTYPE.Mice, Congenic: Mouse strains constructed to possess identical genotypes except for a difference at a single gene locus.Chromosomes, Mammalian: Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of MAMMALS.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.Quantitative Trait Loci: Genetic loci associated with a QUANTITATIVE TRAIT.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.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.Mice, Inbred C57BLRats, Inbred Dahl: Inbred rats derived from Sprague-Dawley rats and used for the study of salt-dependent hypertension. Salt-sensitive and salt-resistant strains have been selectively bred to show the opposite genetically determined blood pressure responses to excess sodium chloride ingestion.Rats, Inbred BNH-2 Antigens: The major group of transplantation antigens in the mouse.Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Mice, Inbred BALB CMice, Inbred DBASpecies Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Mice, Inbred C3HAlleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Mice, Inbred ADisease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.Spleen: An encapsulated lymphatic organ through which venous blood filters.Mice, Inbred NZBMice, Inbred AKRDisease 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.Quantitative Trait, Heritable: A characteristic showing quantitative inheritance such as SKIN PIGMENTATION in humans. (From A Dictionary of Genetics, 4th ed)Rats, Mutant Strains: Rats bearing mutant genes which are phenotypically expressed in the animals.Rats, Inbred LewImmunoglobulin Allotypes: Allelic variants of the immunoglobulin light chains (IMMUNOGLOBULIN LIGHT CHAINS) or heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) encoded by ALLELES of IMMUNOGLOBULIN GENES.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.Genes, MHC Class II: Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and in the I region in mice.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.Epistasis, Genetic: A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.Chromosomes: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Sodium Chloride, Dietary: Sodium chloride used in foods.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.Rats, Inbred SHR: A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.Sialadenitis: INFLAMMATION of salivary tissue (SALIVARY GLANDS), usually due to INFECTION or injuries.Inbreeding: The mating of plants or non-human animals which are closely related genetically.Genetic Loci: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.Rats, Inbred WKY: A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR).Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Complement C5: C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.AKR murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) isolated from spontaneous leukemia in AKR strain mice.Mice, Inbred CBARadiation Chimera: An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Organogold Compounds: Organic compounds that contain GOLD as an integral part of the molecule. Some are used as ANTIRHEUMATIC AGENTS. The term chrysotherapy derives from an ancient Greek term for gold.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.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.Dimercaprol: An anti-gas warfare agent that is effective against Lewisite (dichloro(2-chlorovinyl)arsine) and formerly known as British Anti-Lewisite or BAL. It acts as a chelating agent and is used in the treatment of arsenic, gold, and other heavy metal poisoning.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Antigens, Ly: A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Rats, Inbred OLETF: An inbred strain of Long-Evans rats that develops hyperglycemia, hyperinsulinemia, and mild obesity, mostly in males, that resembles non-insulin-dependent diabetes mellitus in humans. It was developed from outbred Long-Evans stock in 1983.Antigenic Modulation: Loss of detectable antigen from the surface of a cell after incubation with antibodies. This is one method in which some tumors escape detection by the immune system. Antigenic modulation of target antigens also reduces the therapeutic effectiveness of treatment by monoclonal antibodies.Bone Marrow Transplantation: The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.Mice, Inbred MRL lpr: A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.Rats, Inbred BB: A strain of Rattus norvegicus which is a model for spontaneous insulin-dependent diabetes mellitus (DIABETES MELLITUS, INSULIN-DEPENDENT).Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.Lupus Nephritis: Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body.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.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Homozygote: An individual in which both alleles at a given locus are identical.Antigens, Thy-1: A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Rats, Transgenic: Laboratory rats that have been produced from a genetically manipulated rat EGG or rat EMBRYO, MAMMALIAN. They contain genes from another species.Mice, 129 Strain: Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.Radiation Hybrid Mapping: A method for ordering genetic loci along CHROMOSOMES. The method involves fusing irradiated donor cells with host cells from another species. Following cell fusion, fragments of DNA from the irradiated cells become integrated into the chromosomes of the host cells. Molecular probing of DNA obtained from the fused cells is used to determine if two or more genetic loci are located within the same fragment of donor cell DNA.Hybridization, Genetic: The genetic process of crossbreeding between genetically dissimilar parents to produce a hybrid.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.Telemetry: Transmission of the readings of instruments to a remote location by means of wires, radio waves, or other means. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.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.Aminobiphenyl Compounds: Biphenyl compounds substituted in any position by one or more amino groups. Permitted are any substituents except fused rings.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Arthritis, Experimental: ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.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.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.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Rats, 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. This also includes animals with a long history of closed colony breeding.Organ Size: The measurement of an organ in volume, mass, or heaviness.Food Preferences: The selection of one food over another.Friend murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.Leukemia Virus, Murine: Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.Specific Pathogen-Free Organisms: Animals or humans raised in the absence of a particular disease-causing virus or other microorganism. Less frequently plants are cultivated pathogen-free.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Lupus Vulgaris: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the NASAL MUCOSA; BUCCAL MUCOSA; and conjunctival mucosa.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Terpenes: A class of compounds composed of repeating 5-carbon units of HEMITERPENES.Leukemia, Experimental: Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Renin: A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Dinitrobenzenes: Benzene derivatives which are substituted with two nitro groups in the ortho, meta or para positions.Arylamine N-Acetyltransferase: An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.Mice, Inbred CFTR: A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.Rats, Inbred F344Immunogenetics: A subdiscipline of genetics which deals with the genetic basis of the immune response (IMMUNITY).Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Thymus Neoplasms: Tumors or cancer of the THYMUS GLAND.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.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.Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."Skin Transplantation: The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.Sex Characteristics: Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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.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.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Coombs Test: A test to detect non-agglutinating ANTIBODIES against ERYTHROCYTES by use of anti-antibodies (the Coombs' reagent.) The direct test is applied to freshly drawn blood to detect antibody bound to circulating red cells. The indirect test is applied to serum to detect the presence of antibodies that can bind to red blood cells.Antigens, CD45: High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).Splenomegaly: Enlargement of the spleen.

T cell reconstitution of BB/W rats after the initiation of insulitis precipitates the onset of diabetes. (1/252)

One of the diabetes susceptibility genes of the BB/W (Biobreeding/Worcester) rat maps to the lyp locus on chromosome 4. The BB/W lyp allele is responsible for a severe peripheral T lymphopenia. Correction of this lymphopenia by transfer of normal, histocompatible T cells prevents diabetes, providing T cell reconstitution is initiated before insulitis. We have analyzed this time-dependent regulation of the diabetogenic process by normal T cells. We demonstrate that T cell reconstitution after the initiation of insulitis precipitates the onset of diabetes through the recruitment of donor T cells to the autoimmune process. This inability of normal T cells to regulate primed diabetogenic BB/W T cells and their own autoreactive potential were observed when normal T cells outnumbered pathogenic T cells by approximately 1000-fold. Analysis of donor-derived T cells recovered from BB/W rats that were reconstituted before insulitis, and hence protected from diabetes, demonstrates that early T cell reconstitution of BB/W rats does not result in a long term physical or functional depletion of islet cell-specific T cell precursors among donor cells or in the expansion of T cells that can regulate the activation and expansion of diabetogenic T cells.  (+info)

Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. (2/252)

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.  (+info)

Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the "resistant" Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. (3/252)

Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab-mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN) rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 n) rats with Lewis (LEW) (RT1 l) and two reciprocal MHC congenic strains, LEW.1N (RT1n) and BN.1L (RT1 l). This comparison revealed that disease severity and clinical course were strongly influenced by the MHC haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis.  (+info)

Pathological and immunological findings of athymic nude and congenic wild type BALB/c mice experimentally infected with Neospora caninum. (4/252)

Neospora is a cyst-forming coccidian parasite that causes abortions and neuromuscular disorders in a wide variety of mammals. Japanese bovine isolate JPA1 was inoculated intraperitoneally into BALB/c nu/ nu (athymic nude) and BALB/c (congenic wild type) female mice to examine the distribution of parasites and resistance mechanisms to Neospora infection. All the athymic nude mice died within 28 days after intraperitoneal injection of 2 x 10(5) JPA1 tachyzoites, whereas all the congenic wild type mice survived without exhibiting any clinical signs. Tachyzoites were identified in the uterus and pancreas and later spread to many other organs. Most tachyzoites identified in the necrotic foci were localized in the epithelium of the venules and capillaries. Nude mice developed high level of serum interferon-gamma and interleukin-6 as infection proceeded. Inflammatory response to Neospora infection might be mediated by Th1-type dependent cellular immunity.  (+info)

C6 produced by macrophages contributes to cardiac allograft rejection. (5/252)

The terminal components of complement C5b-C9 can cause significant injury to cardiac allografts. Using C6-deficient rats, we have found that the rejection of major histocompatibility (MHC) class I-incompatible PVG.R8 (RT1.A(a)B(u)) cardiac allografts by PVG.1U (RT1.A(u)B(u)) recipients is particularly dependent on C6. This model was selected to determine whether tissue injury results from C6 produced by macrophages, which are a conspicuous component of infiltrates in rejecting transplants. We demonstrated that high levels of C6 mRNA are expressed in isolated populations of macrophages. The relevance of macrophage-produced C6 to cardiac allograft injury was investigated by transplanting hearts from PVG. R8 (C6-) donors to PVG.1U (C6-) rats which had been reconstituted with bone marrow from PVG.1U (C6+) rats as the sole source of C6. Hearts grafted to hosts after C6 reconstitution by bone marrow transplantation underwent rejection characterized by deposition of IgG and complement on the vascular endothelium together with extensive intravascular aggregates of P-selectin-positive platelets. At the time of acute rejection, the cardiac allografts contained extensive perivascular and interstitial macrophage infiltrates. RT-PCR and in situ hybridization demonstrated high levels of C6 mRNA in the macrophage-laden transplants. C6 protein levels were also increased in the circulation during rejection. To determine the relative contribution to cardiac allograft rejection of the low levels of circulating C6 produced systemically by macrophages, C6 containing serum was passively transferred to PVG.1U (C6-) recipients of PVG.R8 (C6-) hearts. This reconstituted the C6 levels to about 3 to 6% of normal values, but failed to induce allograft rejection. In control PVG.1U (C6-) recipients that were reconstituted with bone marrow from PVG.1U (C6-) donors, C6 levels remained undetectable and PVG.R8 cardiac allografts were not rejected. These results indicate that C6 produced by macrophages can cause significant tissue damage.  (+info)

Congenic substitution mapping excludes Sa as a candidate gene locus for a blood pressure quantitative trait locus on rat chromosome 1. (6/252)

Previously, linkage analysis in several experimental crosses between hypertensive rat strains and their contrasting reference strains have identified a major quantitative trait locus (QTL) for blood pressure on rat chromosome 1 (Chr 1) spanning the Sa gene locus. In this study, we report the further dissection of this Chr 1 blood pressure QTL with congenic substitution mapping. To address whether the Sa gene represents a candidate gene for the Chr 1 blood pressure QTL, congenic strains were developed by introgressing high blood pressure QTL alleles from the stroke-prone spontaneously hypertensive rat (SHRSP) into the normotensive Wistar-Kyoto (WKY-1) reference strain. Congenic animals carrying a chromosomal segment from stroke-prone spontaneously hypertensive rats between genetic markers Mt1pa and D1Rat200 (including the Sa gene locus) show a significant increase in basal systolic and diastolic blood pressure compared with their normotensive Wistar-Kyoto progenitors (P<0.001, respectively), whereas congenic animals carrying a subfragment of this Chr 1 region defined by markers Mt1pa and D1Rat57 (also spanning the Sa gene) do not show elevated basal blood pressure levels (P=0.83 and P=0.9, respectively). Similar results were obtained for NaCl-induced blood pressure values. Thus, the blood pressure QTL on Chr 1 is located centromeric to the Sa gene locus in a region that is syntenic to human chromosome 11p15.4-p15.3. This region excludes the Sa as a blood pressure-elevating candidate gene locus on the basis of congenic substitution mapping approaches.  (+info)

Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. (7/252)

A CD4(+) T cell subpopulation defined by the expression levels of a particular cell surface molecule (e.g. CD5, CD45RB, CD25, CD62L or CD38) bears an autoimmune-preventive activity in various animal models. Here we show that the expression of CD25 is highly specific, when compared with other molecules, in delineating the autoimmune-preventive immunoregulatory CD4(+) T cell population. Furthermore, although CD25 is an activation marker for T cells, the following findings indicate that immunoregulatory CD25(+)CD4(+) T cells are functionally distinct from activated or anergy-induced T cells derived from CD25(-)CD4(+) T cells. First, the former are autoimmune-preventive in vivo, naturally unresponsive (anergic) to TCR stimulation in vitro and, upon TCR stimulation, able to suppress the activation/proliferation of other T cells, whereas the latter scarcely exhibit the in vivo autoimmune-preventive activity or the in vitro suppressive activity. Second, such activated or anergy-induced CD25(-) spleen cells produce various autoimmune diseases when transferred to syngeneic athymic nude mice, whereas similarly treated normal spleen cells, which include CD25(+)CD4(+) T cells, do not. Third, upon polyclonal T cell stimulation, CD25(+)CD4(+) T cells express CD25 at higher levels and more persistently than CD25(-)CD4(+) T cell-derived activated T cells; moreover, when the stimulation is ceased, the former revert to the original levels of CD25 expression, whereas the latter lose the expression. These results collectively indicate that naturally anergic and suppressive CD25(+)CD4(+) T cells present in normal naive mice are functionally and phenotypically stable, distinct from other T cells, and play a key role in maintaining immunologic self-tolerance.  (+info)

Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene in GK rats. (8/252)

Genetic analysis of the diabetic GK rat has revealed several diabetes susceptibility loci. Congenic strains have been established for the major diabetes locus, Niddm1, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Niddm1 was dissected into two subloci, physically separated in the congenic strains Niddm1b and Niddm1i, each with at least one disease susceptibility gene. Here we have mapped Niddm1b to 1 cM by genetic and pathophysiological characterization of new congenic substrains for the locus. The gene encoding insulin-degrading enzyme (IDE:) was located to this 1 cM region, and the two amino acid substitutions (H18R and A890V) identified in the GK allele reduced insulin-degrading activity by 31% in transfected cells. However, when the H18R and A890V variants were studied separately, no effects were observed, demonstrating a synergistic effect of the two variants on insulin degradation. No effect on insulin degradation was observed in cell lysates, indicating that the effect is coupled to receptor-mediated internalization of insulin. Congenic rats with the IDE: GK allele displayed post-prandial hyperglycemia, reduced lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake and reduced insulin degradation in isolated muscle. Analysis of additional rat strains demonstrated that the dysfunctional IDE: allele was unique to GK. These data point to an important role for IDE: in the diabetic phenotype in GK.  (+info)

  • The congenic segment is approximately 25 cM in length, extending from D7Mit213 to D7Mit41, and includes the tub, Ucp2 and Ucp3, genes, all of which are candidate genes for this effect. (
  • This presentation will compare ABR results in the two congenic strains as well as compare the present data with the previous inbred C57BL/6J and CBA/CaJ data. (
  • Thus, to further study MMU2, congenic strains were developed by introgressing CAST/EiJ segments into the backgrounds of HG and C57BL/6J (B6) to fine map QTL identified by Corva et al. (
  • Based upon the clinical, immunological, and genetic components, the most appropriate animal models for RA seem to be (i) those that use genetically controlled systemic autoimmune joint diseases, (ii) those in which the MHC (class II molecules) plays a crucial role, (iii) those in which both T and B cells are involved, and (iv) those that apply (auto)antigenic molecules of cartilage or joint tissues for provoking ("targeting") synovial joint inflammation. (
  • In this review, we summarize the current literature regarding the role of Nox in focal ischemic injury and discuss critical issues that should be considered when investigating Nox-related pathophysiology in animal models of stroke. (
  • The increasing prevalence of these diseases in the human population makes the genetic and phenotypic characterizations of these mutant animals a leading area of interest in the biomedical community. (
  • Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and alpha mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the alpha mating type to increased virulence in congenic serotype D strains. (
  • As a consequence, there are many experimental animal models attempting to mimic the multiple clinical symptoms of RA. (
  • While the various animal models are tremendously helpful for investigating certain aspects of the human disease, none of these models recreates the full spectrum of diseases collectively called RA. (
  • Notably, thousands of investigators and pharmaceutical companies use animal models of RA, perhaps without understanding the differences among the different subtypes of this disease and the corresponding animal models [ 2 - 5 ]. (
  • In comparison, normotensive animals, beyond their usefulness as controls for hypertensive models, have received little recognition capable of unmasking critical mechanisms that can prevent hypertension. (
  • The use of animal models in research resulted in the advancement of knowledge for how diseases affect animals and humans. (
  • Early identification of drugs that will fail testing in higher level animal models or clinical trials, lowers the over-all cost of drug development. (
  • The FDA relies on data generated from animal models to assess efficacy and safety of new drug entities. (
  • This new edition of Animal Models in Cardiovascular Research describes historical and recent advances in our understanding of the cardiovascular system from studies conducted in a variety of animal models. (
  • This third edition is designed to provide a better basis for understanding and using animal models in the current climate of background knowledge and information. (
  • Focusing on comparisons and usefulness of the animal models, the chapters describe a variety of research avenues, such as modeling cognitive and degenerative disorders in fruit flies, congenic mouse strains for candidate disease gene identification in complex traits, nonhuman primate models for AIDS, and animal models of prostate cancer. (
  • Our research utilizes genetic animal models to study simple and complex addiction-related traits. (
  • Animal models have elucidated the cellular pathological sequelae of specific inner ear insults [ 10 ]. (
  • A discussion of the application of animal models to the study of the effects of heredity on the human response to chemicals was presented in this paper. (
  • The authors conclude that animal models are extremely helpful in the study of the human response to chemicals. (
  • Animal experimentation and the models by which it is conducted are a core component of the Preclinical Translational Research Unit's work. (
  • Animal models are the primary mode of research responsible for translating preclinical project work into successful clinical trials, which is why they are a focus of our unit. (
  • We work to create animal models that minimize the consumption of resources, especially time and money, without allowing for any compromise in the integrity of our data or their reproducibility. (
  • By continually striving to uphold these standards while continually striving to assess and improve our animal models we ensure that we consistently deliver optimum results and solutions. (
  • Importantly, selective inhibition of this enzyme reduces adenocarcinoma formation and cancer progression in preclinical animal models ( 6 -8 ). (
  • Studies with specific inhibitors of COX-2 enzyme have shown significant effects in reducing the incidence and progression of tumors in both animal models and in treatment of cancer patients ( 6 -8 ). (
  • By selectively breeding individuals containing more of the recipient genome from each generation, our speed congenics program, Marker-Assisted Accelerated Backcrossing (MAX-BAX ® ), can deliver a fully congenic colony in only 15 months. (
  • Animal studies may help to fill the gaps in human genome-wide association studies (GWAS) by allowing for gene mapping and functional studies, which cannot be performed in human patients and may yield greater insights into the mechanisms of autoimmune T and B cell responses in RA [ 2 - 4 ]. (
  • Blue bars at the bottom of the map represent the congenic segments from CAST/EiJ introgressed onto the BLSW genetic background (red lines). (
  • Refined genotyping of two congenic lines 10.R and 10.2 delimited the ahl5 critical interval in a 2.19 Mbp region (red box) defined by markers D10Ntra205 and D10Ntra222 . (
  • 2011. Single nucleotide polymorphism analysis of chicken genetic resources: Variation within and among MHC-congenic lines and mapping of developmental mutations. (
  • By use of an inbred recurrent line with backcrossing and selection in single-family replicate lines, these lines will become congenic to the recurrent parent, except for QTL of large effect and closely linked regions of the genome. (
  • The effect is demonstrated in more than one animal species expected to react with a response predictive for humans, unless the effect is demonstrated in a single animal species that represents a sufficiently well-characterized animal model for predicting the response in humans. (
  • The animal study endpoint is clearly related to the desired benefit in humans, generally the enhancement of survival or prevention of major morbidity. (
  • The data or information on the kinetics and pharmacodynamics of the product or other relevant data or information, in animals and humans, allows selection of an effective dose in humans. (
  • Toxoplasma gondii is an extremely widespread intracellular protozoan parasite that establishes long-lasting infection in humans and animals. (
  • WNV is maintained in a natural cycle between mosquitoes and birds but also infects humans, horses, and other animals. (
  • The molecular basis of WNV infection in humans and other animals is not clearly established. (
  • Background Flt3-ligand is a cytokine that induces relatively slow mobilization of hematopoietic cells in animals and humans in vivo . (
  • Alone, or in combination with other growth factors, FL stimulates the proliferation of highly enriched human and murine HSC in vitro and leads to expansion and mobilization of progenitor cells in animals and humans in vitro . (
  • Migration of transferred cells has been studied mainly by tissue biopsies in humans or harvesting organs in animals to determine the presence of donor cells. (
  • The Foundation for Biomedical Research website has a table listing the animals behind top drugs and a comprehensive summary of how animal testing and research has advanced human health. (
  • The use of animals in biomedical research dates back to approximately the 6th-5th century BC with more prominent references in the writings of Aristotle, Diocles, Praxagoras in the 4th century BC and Erasistratus and Herophilus in the 4th-3rd century BC 1 . (
  • Thus bilaterally nephrectomized SHR × WKY F1 animals that receive a kidney from the SHR develop a BP that is significantly greater than that of animals that receive a kidney from the WKY rat, even when the SHR donor is young (prehypertensive) or has been pretreated since weaning with anti-hypertensive drugs to prevent secondary effects due to renal damage ( 21 ). (
  • Practical training takes place on the animal and includes handling, measurement of physiological basic data, marking, section and killing methods. (
  • Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. (