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Phenotypes Associated with This Genotype
Genotype
MGI:5661482
Allelic
Composition
Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival is about 50 weeks and all mice show a general deterioration of health, especially weight loss
• 70% lethality by one year of age

immune system
• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis indicating defective negative selection
• CD8+ T cells exhibit increased proliferation in response to syngeneic stimulators
• however, CD4 T cells show little proliferation like controls in response to syngeneic stimulators
• T cells show reduced proliferation compared to controls in response to allogeneic stimulators
• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis accompanying negative selection
• decrease in proportion of double positive thymocytes
• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen
• the CD4 to CD8 T cell ratio is somewhat skewed in favor of CD4 T cells
• mice show an increase in mature CD4 T cell numbers
• mice show a higher proportion of previously activated, anergic CD4 T cells
• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen
• increase in CD44hiCD62Lhi central memory CD8 T cells
• greater Foxp3+ Treg cell proportions and numbers in both the thymus and lymph nodes
• most of the increase in total Treg number is due to an increase in CD25-negative cells
• aged mice exhibit increased numbers of both cD25+ and CD25- Treg cells in lymphoid organs, making up about 50% of all CD4 T cells
• accumulation of activated, autoreactive T cells
• CD4 and CD8 T cells in aged mice are highly activated
• starting at 20 weeks of age, accumulation of activated T cells is seen in the peripheral blood which becomes very dramatic and ubiquitous at 40-50 weeks of age
• only IFN-gamma and not IL-17 or IL-4 are increased, suggesting that activated T cells are Th1 polarized
• increase in proportion of single positive thymocytes
• however, only the absolute single positive cell numbers are increased, especially for CD4 single positive, while the double positive cell number is comparable to controls
• all mice show severe splenomegaly between 45 and 60 weeks of age
• spleen shows an increase in both T and B cells and a large increase in CD3-B220- myeloid/other cells
• mesenteric lymph nodes show an increase in both T and B cells and a large increase in CD3-B220- myeloid/other cells
• all mice show severe lymphadenopathy between 45 and 60 weeks of age
• activated CD4 T cells in aged mice have increased effector function, as splenic CD4 T cells from 50 week old mice secrete increased amounts of IFN-gamma
• mice exhibit multi-organ autoimmunity
• autoantibodies against multiple non-lymphoid tissues (pancreas, eye, lung, liver, kidney, stomach) are detected in 40-50 week old mice
• a few mice exhibit an increase in anti-nuclear antibodies (ANA)
• mice show significant infiltration of lymphocytes into the liver
• mice show significant infiltration of lymphocytes into the kidney
• a few mice with high levels of ANA show disruption of kidney morphology that looks like glomerulonephritis
• mice show significant infiltration of lymphocytes into the lung
• some mice develop a severe inflammatory skin condition

hematopoietic system
• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis indicating defective negative selection
• CD8+ T cells exhibit increased proliferation in response to syngeneic stimulators
• however, CD4 T cells show little proliferation like controls in response to syngeneic stimulators
• T cells show reduced proliferation compared to controls in response to allogeneic stimulators
• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis accompanying negative selection
• decrease in proportion of double positive thymocytes
• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen
• the CD4 to CD8 T cell ratio is somewhat skewed in favor of CD4 T cells
• mice show an increase in mature CD4 T cell numbers
• mice show a higher proportion of previously activated, anergic CD4 T cells
• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen
• increase in CD44hiCD62Lhi central memory CD8 T cells
• greater Foxp3+ Treg cell proportions and numbers in both the thymus and lymph nodes
• most of the increase in total Treg number is due to an increase in CD25-negative cells
• aged mice exhibit increased numbers of both cD25+ and CD25- Treg cells in lymphoid organs, making up about 50% of all CD4 T cells
• accumulation of activated, autoreactive T cells
• CD4 and CD8 T cells in aged mice are highly activated
• starting at 20 weeks of age, accumulation of activated T cells is seen in the peripheral blood which becomes very dramatic and ubiquitous at 40-50 weeks of age
• only IFN-gamma and not IL-17 or IL-4 are increased, suggesting that activated T cells are Th1 polarized
• increase in proportion of single positive thymocytes
• however, only the absolute single positive cell numbers are increased, especially for CD4 single positive, while the double positive cell number is comparable to controls
• large increase in CD3-B220- myeloid/other cells in the mesenteric lymph nodes and spleen; large proportion of these cells are Ly6cLoCD11b+ neutrophils, indicating increased inflammation
• all mice show severe splenomegaly between 45 and 60 weeks of age
• spleen shows an increase in both T and B cells and a large increase in CD3-B220- myeloid/other cells

cellular
• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis indicating defective negative selection
• CD8+ T cells exhibit increased proliferation in response to syngeneic stimulators
• however, CD4 T cells show little proliferation like controls in response to syngeneic stimulators
• T cells show reduced proliferation compared to controls in response to allogeneic stimulators

endocrine/exocrine glands
• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis indicating defective negative selection

liver/biliary system
• mice show significant infiltration of lymphocytes into the liver

integument
• some mice develop a severe inflammatory skin condition

renal/urinary system
• mice show significant infiltration of lymphocytes into the kidney
• a few mice with high levels of ANA show disruption of kidney morphology that looks like glomerulonephritis

respiratory system
• mice show significant infiltration of lymphocytes into the lung

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
autoimmune hypersensitivity disease DOID:417 OMIM:109100
OMIM:607836
OMIM:613551
J:217939


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
01/14/2020
MGI 6.14
The Jackson Laboratory