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Phenotypes Associated with This Genotype
Genotype
MGI:3714292
Allelic
Composition
Ctla4tm1Shr/Ctla4tm1Shr
Genetic
Background
either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (53 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die at approximately 3-4 weeks of age

hematopoietic system
• vigorous spontaneous proliferation of lymph node cells is seen in culture, with moderate proliferation of spleen cells in culture, compared to no spontaneous proliferation of cultured wild-type cells; ~80% of cells are CD4+CD8- single-positive cells and 20% are CD4-CD8+ single-positives after 6 days in culture
• massive splenomegaly observed in 15 to 20-day old mice
• mutant T cells are larger than wild-type T cells
• increase is seen in percentage and expression levels of activation markers CD69, CD25, and CD44 on T cells in spleen and lymph nodes
• mutant T cells are larger than wild-type T cells
• 10-fold decrease in percentage of double-positive CD4+CD8+ T cell in thymus is observed
• relative increase in numbers of CD3+CD4+ and CD3+CD8+ single-positive T cells is seen in thymus
• there is a 5-fold increase in CD4-CD8- double-negative cells in the thymus in 15 to 20-day old mice
• increase in percentage and absolute number of CD3+ cells
• significant decrease in Mel-14+ (naive) T cells in spleen

immune system
• destructive myocarditis is seen with massive interstitial infiltrates consisting of abundant CD3+ cells, CD4+ and CD8+ cells, numerous macrophages, and occasional B220+ B cells, as well as neutrophils in mice at ~15 days of age
• vigorous spontaneous proliferation of lymph node cells is seen in culture, with moderate proliferation of spleen cells in culture, compared to no spontaneous proliferation of cultured wild-type cells; ~80% of cells are CD4+CD8- single-positive cells and 20% are CD4-CD8+ single-positives after 6 days in culture
• some interstitial mononuclear infiltrates in absence of tissue destruction
• severe pancreatitis is seen with intense mononuclear infiltrate with destruction of islets and glandular elements; infiltrates consist of abundant CD3+ cells, CD4+ and CD8+ cells, numerous macrophages, and occasional B220+ B cells at ~15 days of age
• massive splenomegaly observed in 15 to 20-day old mice
• mutant T cells are larger than wild-type T cells
• increase is seen in percentage and expression levels of activation markers CD69, CD25, and CD44 on T cells in spleen and lymph nodes
• mutant T cells are larger than wild-type T cells
• 10-fold decrease in percentage of double-positive CD4+CD8+ T cell in thymus is observed
• relative increase in numbers of CD3+CD4+ and CD3+CD8+ single-positive T cells is seen in thymus
• there is a 5-fold increase in CD4-CD8- double-negative cells in the thymus in 15 to 20-day old mice
• increase in percentage and absolute number of CD3+ cells
• significant decrease in Mel-14+ (naive) T cells in spleen
• increase in percentage and absolute number of CD3+ cells at ~15 days of age
• significant decrease in Mel-14+ (naive) T cells in spleen
• massive lymphadenopathy found, with up to 10-fold more lymph node cells in mutants
• analysis of supernatants from anti-CD3-stimulated lymph node and spleen cells show increased amounts of interferon gamma (Ifng), interleukin-4 (Il-4), and granulocyte-macrophage colony-stimulating factor compared to cells from wild-type mice
• synovitis observed in some mice
• some interstitial mononuclear infiltrates in absence of tissue destruction are seen

endocrine/exocrine glands
• some interstitial mononuclear infiltrates in absence of tissue destruction
• severe pancreatitis is seen with intense mononuclear infiltrate with destruction of islets and glandular elements; infiltrates consist of abundant CD3+ cells, CD4+ and CD8+ cells, numerous macrophages, and occasional B220+ B cells at ~15 days of age

cardiovascular system
• in some mice
• destructive myocarditis is seen with massive interstitial infiltrates consisting of abundant CD3+ cells, CD4+ and CD8+ cells, numerous macrophages, and occasional B220+ B cells, as well as neutrophils in mice at ~15 days of age

digestive/alimentary system
• some interstitial mononuclear infiltrates in absence of tissue destruction

respiratory system
• some interstitial mononuclear infiltrates in absence of tissue destruction are seen

skeleton
• synovitis observed in some mice

growth/size/body
• massive splenomegaly observed in 15 to 20-day old mice

cellular
• vigorous spontaneous proliferation of lymph node cells is seen in culture, with moderate proliferation of spleen cells in culture, compared to no spontaneous proliferation of cultured wild-type cells; ~80% of cells are CD4+CD8- single-positive cells and 20% are CD4-CD8+ single-positives after 6 days in culture


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
05/07/2024
MGI 6.23
The Jackson Laboratory