Phenotypes Associated with This Genotype

Genotype
MGI:3723019

• Allelic Composition: E2f2^tm1Zubi/E2f2^tm1Zubi
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

mortality/aging

premature death ( J:76318 )

• at 15 months, only 27% of mice are alive compared to 67% of wild-type mice

immune system

abnormal immune system morphology ( J:76318 )

enlarged spleen ( J:76318 )

• at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice

increased spleen weight ( J:76318 )

• at week 8 to 12, spleen weight is increased 2-fold (1445+/-250 mg) relative to in wild-type mice (668+/-108 mg) and continues to increase at 15 months (3340+/-540 mg compared to 722+/-125 mg in wild-type mice)

abnormal T cell differentiation ( J:76318 )

• the fraction of mature (CD4+ and, especially, CD8+) thymocytes in the thymus is increased with a decreased in immature double positive thymocytes

abnormal T cell subpopulation ratio ( J:76318 )

• there is an increase in the number of CD8+ T cells relative to CD4+ T cells (CD4+/CD8+ ratio: 0.79+/-0.1 compared to 1.43+/-0.3 in wild-type mice)

• however, the T to B cells ratio is normal

increased memory T cell number ( J:76318 )

• at 3 to 4 weeks and at 15 months, the number of CD44^hiCD69- memory T cells is increased

abnormal spleen white pulp morphology ( J:76318 )

• at 15 months, mice display white pulp hyperplasia and increased sinusoidal cellularity

abnormal immune system physiology ( J:76318 )

increased T cell proliferation ( J:76318 )

• in response to IL-2 treatment, effector/memory cell (CD44^hiCD69-) T cell proliferation is increased relative to in wild-type mice by 2 times at weeks 8 to 12, and 13 times at 15 months

• T cell proliferation stimulated by CD3 antibody is increased compared to in stimulated wild-type mice and is more prominent at suboptimal CD3 antibody concentrations

increased susceptibility to autoimmune disorder ( J:76318 )

• at 15 months, mice exhibit features of autoimmune disease including inflammatory infiltrate, adnormal accumulation of effector/memory T cells, and double stranded DNA antibodies

increased anti-double stranded DNA antibody level ( J:76318 )

• the amount of double stranded DNA antibodies is increased relative to in wild-type mice and corresponds to the severity of organ damage

increased inflammatory response ( J:76318 )

• at 15 months, mice exhibit features of autoimmune disease

• in elderly mice, increased mononuclear infiltrate is observed in the lung, kidney and liver

liver inflammation ( J:76318 )

• in elderly mice, inflammatory infiltrate accumulates in the liver and perivascular infiltrates are observed

glomerulonephritis ( J:76318 )

• elderly mice exhibit membranoproliferative glomerulonephritis that is focal and of moderate intensity

• affected glomeruli are enlarged with a thickened basement membrane and contain perivascular aggregates of inflammatory infiltrate and immune complex deposition

lung inflammation ( J:76318 )

• in elderly mice, inflammatory infiltrate accumulates in the lung

liver/biliary system

liver inflammation ( J:76318 )

• in elderly mice, inflammatory infiltrate accumulates in the liver and perivascular infiltrates are observed

renal/urinary system

glomerulonephritis ( J:76318 )

• elderly mice exhibit membranoproliferative glomerulonephritis that is focal and of moderate intensity

• affected glomeruli are enlarged with a thickened basement membrane and contain perivascular aggregates of inflammatory infiltrate and immune complex deposition

increased renal glomerulus basement membrane thickness ( J:76318 )

• affected glomeruli display a thickened basement membrane

renal glomerular immunoglobulin deposits ( J:76318 )

renal glomerulus hypertrophy ( J:76318 )

• affected glomeruli are enlarged

respiratory system

lung inflammation ( J:76318 )

• in elderly mice, inflammatory infiltrate accumulates in the lung

hematopoietic system

increased T cell proliferation ( J:76318 )

• in response to IL-2 treatment, effector/memory cell (CD44^hiCD69-) T cell proliferation is increased relative to in wild-type mice by 2 times at weeks 8 to 12, and 13 times at 15 months

• T cell proliferation stimulated by CD3 antibody is increased compared to in stimulated wild-type mice and is more prominent at suboptimal CD3 antibody concentrations

enlarged spleen ( J:76318 )

• at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice

increased spleen weight ( J:76318 )

• at week 8 to 12, spleen weight is increased 2-fold (1445+/-250 mg) relative to in wild-type mice (668+/-108 mg) and continues to increase at 15 months (3340+/-540 mg compared to 722+/-125 mg in wild-type mice)

abnormal T cell differentiation ( J:76318 )

• the fraction of mature (CD4+ and, especially, CD8+) thymocytes in the thymus is increased with a decreased in immature double positive thymocytes

abnormal T cell subpopulation ratio ( J:76318 )

• there is an increase in the number of CD8+ T cells relative to CD4+ T cells (CD4+/CD8+ ratio: 0.79+/-0.1 compared to 1.43+/-0.3 in wild-type mice)

• however, the T to B cells ratio is normal

increased memory T cell number ( J:76318 )

• at 3 to 4 weeks and at 15 months, the number of CD44^hiCD69- memory T cells is increased

abnormal spleen white pulp morphology ( J:76318 )

• at 15 months, mice display white pulp hyperplasia and increased sinusoidal cellularity

cellular

abnormal cell physiology ( J:75726 )

• adenovirus-Myc fails to induce S phase as it does in wild-type mouse embryonic fibroblasts

abnormal cell death ( J:75726 )

• cell death induced by Myc expression in primary fibroblast cells is somewhat less efficient than in wild-type primary fibroblast

increased T cell proliferation ( J:76318 )

• in response to IL-2 treatment, effector/memory cell (CD44^hiCD69-) T cell proliferation is increased relative to in wild-type mice by 2 times at weeks 8 to 12, and 13 times at 15 months

• T cell proliferation stimulated by CD3 antibody is increased compared to in stimulated wild-type mice and is more prominent at suboptimal CD3 antibody concentrations

integument

progressive hair loss ( J:76318 )

• elderly mice exhibit considerable hair loss

abnormal skin morphology ( J:76318 )

• elderly mice exhibit skin wounds

reddish skin ( J:76318 )

• elderly mice exhibit erythema affecting the head and neck

growth/size/body

enlarged spleen ( J:76318 )

• at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice

increased spleen weight ( J:76318 )

• at week 8 to 12, spleen weight is increased 2-fold (1445+/-250 mg) relative to in wild-type mice (668+/-108 mg) and continues to increase at 15 months (3340+/-540 mg compared to 722+/-125 mg in wild-type mice)