Phenotypes associated with this allele

• Allele Symbol: Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt
• Allele Name: transgene insertion A, Astar Winoto
• Allele ID: MGI:5661474
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(CD2-TcraF5,CD2-TcrbF5)1Kio/0 Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0	involves: C57BL/6 * C57BL/10	MGI:5661486
cx2	Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0 Tg(Nr4a1-EGFP/cre)820Khog/0	involves: C57BL/6 * C57BL/6J	MGI:5661492
cx3	Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0 Tg(TcraH-Y,TcrbH-Y)71Vbo/0	involves: C57BL/6 * C57BL/6J * DBA/2J	MGI:5661488
tg4	Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0	involves: C57BL/6	MGI:5661482
tg5	Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0	involves: C57BL/6 * CBA/J	MGI:5661494

Genotype
MGI:5661486

cx1

• Allelic Composition: Tg(CD2-TcraF5,CD2-TcrbF5)1Kio/0; Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0
• Genetic Background: involves: C57BL/6 * C57BL/10

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to injection with the F5 TCR-specific peptide NP compared to controls which show massive apoptosis

abnormal T cell clonal deletion ( J:217939 )

• thymocyte apoptosis is inhibited in response to injection with the F5 TCR-specific peptide NP compared to controls which show massive apoptosis indicating impaired clonal deletion

increased T cell number ( J:217939 )

enlarged lymph nodes ( J:217939 )

• lymphoid organs are mildly enlarged

hematopoietic system

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to injection with the F5 TCR-specific peptide NP compared to controls which show massive apoptosis

abnormal T cell clonal deletion ( J:217939 )

• thymocyte apoptosis is inhibited in response to injection with the F5 TCR-specific peptide NP compared to controls which show massive apoptosis indicating impaired clonal deletion

increased T cell number ( J:217939 )

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to injection with the F5 TCR-specific peptide NP compared to controls which show massive apoptosis

cellular

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to injection with the F5 TCR-specific peptide NP compared to controls which show massive apoptosis

Genotype
MGI:5661492

cx2

• Allelic Composition: Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0; Tg(Nr4a1-EGFP/cre)820Khog/0
• Genetic Background: involves: C57BL/6 * C57BL/6J

immune system

decreased thymocyte apoptosis ( J:217939 )

• mice exhibit a defect in thymocyte negative selection, showing an increase in the proportion of post-selection DP thymocytes which indicates rescue of these cells from death

abnormal T cell clonal deletion ( J:217939 )

• mice exhibit a defect in thymocyte negative selection, showing an increase in the proportion of post-selection DP thymocytes which indicates rescue of these cells from death/clonal deletion

hematopoietic system

decreased thymocyte apoptosis ( J:217939 )

• mice exhibit a defect in thymocyte negative selection, showing an increase in the proportion of post-selection DP thymocytes which indicates rescue of these cells from death

abnormal T cell clonal deletion ( J:217939 )

• mice exhibit a defect in thymocyte negative selection, showing an increase in the proportion of post-selection DP thymocytes which indicates rescue of these cells from death/clonal deletion

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:217939 )

• mice exhibit a defect in thymocyte negative selection, showing an increase in the proportion of post-selection DP thymocytes which indicates rescue of these cells from death

cellular

decreased thymocyte apoptosis ( J:217939 )

• mice exhibit a defect in thymocyte negative selection, showing an increase in the proportion of post-selection DP thymocytes which indicates rescue of these cells from death

Genotype
MGI:5661488

cx3

• Allelic Composition: Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0; Tg(TcraH-Y,TcrbH-Y)71Vbo/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2J

immune system

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to an HY TCR-specific peptide compared to controls which show massive apoptosis

abnormal T cell clonal deletion ( J:217939 )

• thymocytes are protected from apoptosis induced by an HY TCR-specific peptide indicating impaired clonal deletion

hematopoietic system

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to an HY TCR-specific peptide compared to controls which show massive apoptosis

abnormal T cell clonal deletion ( J:217939 )

• thymocytes are protected from apoptosis induced by an HY TCR-specific peptide indicating impaired clonal deletion

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to an HY TCR-specific peptide compared to controls which show massive apoptosis

cellular

decreased thymocyte apoptosis ( J:217939 )

• thymocyte apoptosis is inhibited in response to an HY TCR-specific peptide compared to controls which show massive apoptosis

Genotype
MGI:5661482

tg4

• Allelic Composition: Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0
• Genetic Background: involves: C57BL/6

mortality/aging

premature death ( J:217939 )

• 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

decreased thymocyte apoptosis ( J:217939 )

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

abnormal T cell proliferation ( J:217939 )

• 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

enlarged spleen ( J:217939 )

• all mice show severe splenomegaly between 45 and 60 weeks of age

abnormal T cell clonal deletion ( J:217939 )

• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis accompanying negative selection

decreased double-positive T cell number ( J:217939 )

• decrease in proportion of double positive thymocytes

increased B cell number ( J:217939 )

• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen

abnormal T cell subpopulation ratio ( J:217939 )

• the CD4 to CD8 T cell ratio is somewhat skewed in favor of CD4 T cells

abnormal CD4-positive, alpha-beta T cell number ( J:217939 )

• mice show an increase in mature CD4 T cell numbers

• mice show a higher proportion of previously activated, anergic CD4 T cells

increased T cell number ( J:217939 )

• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen

increased central memory CD8 positive, alpha-beta T cell number ( J:217939 )

• increase in CD44hiCD62Lhi central memory CD8 T cells

increased regulatory T cell number ( J:217939 )

• 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

increased activated T cell number ( J:217939 )

• 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

increased single-positive T cell number ( J:217939 )

• 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

abnormal splenic cell ratio ( J:217939 )

• spleen shows an increase in both T and B cells and a large increase in CD3-B220- myeloid/other cells

abnormal mesenteric lymph node morphology ( J:217939 )

• mesenteric lymph nodes show an increase in both T and B cells and a large increase in CD3-B220- myeloid/other cells

enlarged lymph nodes ( J:217939 )

• all mice show severe lymphadenopathy between 45 and 60 weeks of age

lymphoid hyperplasia ( J:217939 )

increased interferon-gamma secretion ( J:217939 )

• 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

increased susceptibility to autoimmune disorder ( J:217939 )

• mice exhibit multi-organ autoimmunity

increased autoantibody level ( J:217939 )

• autoantibodies against multiple non-lymphoid tissues (pancreas, eye, lung, liver, kidney, stomach) are detected in 40-50 week old mice

increased anti-nuclear antigen antibody level ( J:217939 )

• a few mice exhibit an increase in anti-nuclear antibodies (ANA)

liver inflammation ( J:217939 )

• mice show significant infiltration of lymphocytes into the liver

kidney inflammation ( J:217939 )

• mice show significant infiltration of lymphocytes into the kidney

glomerulonephritis ( J:217939 )

• a few mice with high levels of ANA show disruption of kidney morphology that looks like glomerulonephritis

lung inflammation ( J:217939 )

• mice show significant infiltration of lymphocytes into the lung

skin inflammation ( J:217939 )

• some mice develop a severe inflammatory skin condition

hematopoietic system

decreased thymocyte apoptosis ( J:217939 )

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

abnormal T cell proliferation ( J:217939 )

• 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

enlarged spleen ( J:217939 )

• all mice show severe splenomegaly between 45 and 60 weeks of age

abnormal T cell clonal deletion ( J:217939 )

• in response to anti-CD3 and anti-CD28 antibody stimulation, thymocytes show increased resistance to apoptosis accompanying negative selection

decreased double-positive T cell number ( J:217939 )

• decrease in proportion of double positive thymocytes

increased B cell number ( J:217939 )

• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen

abnormal T cell subpopulation ratio ( J:217939 )

• the CD4 to CD8 T cell ratio is somewhat skewed in favor of CD4 T cells

abnormal CD4-positive, alpha-beta T cell number ( J:217939 )

• mice show an increase in mature CD4 T cell numbers

• mice show a higher proportion of previously activated, anergic CD4 T cells

increased T cell number ( J:217939 )

• increase in numbers of both T cells and B cells, especially in the mesenteric lymph nodes and spleen

increased central memory CD8 positive, alpha-beta T cell number ( J:217939 )

• increase in CD44hiCD62Lhi central memory CD8 T cells

increased regulatory T cell number ( J:217939 )

• 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

increased activated T cell number ( J:217939 )

• 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

increased single-positive T cell number ( J:217939 )

• 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

increased myeloid cell number ( J:217939 )

• 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

abnormal splenic cell ratio ( J:217939 )

• spleen shows an increase in both T and B cells and a large increase in CD3-B220- myeloid/other cells

cellular

decreased thymocyte apoptosis ( J:217939 )

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

abnormal T cell proliferation ( J:217939 )

• 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

decreased thymocyte apoptosis ( J:217939 )

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

liver/biliary system

liver inflammation ( J:217939 )

• mice show significant infiltration of lymphocytes into the liver

integument

skin inflammation ( J:217939 )

• some mice develop a severe inflammatory skin condition

renal/urinary system

kidney inflammation ( J:217939 )

• mice show significant infiltration of lymphocytes into the kidney

glomerulonephritis ( J:217939 )

• a few mice with high levels of ANA show disruption of kidney morphology that looks like glomerulonephritis

respiratory system

lung inflammation ( J:217939 )

• mice show significant infiltration of lymphocytes into the lung

growth/size/body

enlarged spleen ( J:217939 )

• all mice show severe splenomegaly between 45 and 60 weeks of age

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

Genotype
MGI:5661494

tg5

• Allelic Composition: Tg(Cd4-BCL2*G101A*D102A*D103A)AWnt/0
• Genetic Background: involves: C57BL/6 * CBA/J

immune system

decreased thymocyte apoptosis ( J:217939 )

• superantigen negative selection is defective, with mice showing increased proportions of Vbeta5, Vbeta6, and Vbeta11 expressing SP thymocytes indicating enhanced rescue of thymocytes from negative selection

abnormal T cell clonal deletion ( J:217939 )

• superantigen negative selection is defective, with mice showing increased proportions of Vbeta5, Vbeta6, and Vbeta11 expressing SP thymocytes indicating impaired clonal deletion

hematopoietic system

decreased thymocyte apoptosis ( J:217939 )

• superantigen negative selection is defective, with mice showing increased proportions of Vbeta5, Vbeta6, and Vbeta11 expressing SP thymocytes indicating enhanced rescue of thymocytes from negative selection

abnormal T cell clonal deletion ( J:217939 )

• superantigen negative selection is defective, with mice showing increased proportions of Vbeta5, Vbeta6, and Vbeta11 expressing SP thymocytes indicating impaired clonal deletion

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:217939 )

• superantigen negative selection is defective, with mice showing increased proportions of Vbeta5, Vbeta6, and Vbeta11 expressing SP thymocytes indicating enhanced rescue of thymocytes from negative selection

cellular

decreased thymocyte apoptosis ( J:217939 )

• superantigen negative selection is defective, with mice showing increased proportions of Vbeta5, Vbeta6, and Vbeta11 expressing SP thymocytes indicating enhanced rescue of thymocytes from negative selection