immune system phenotype

• abnormal T cell subpopulation ratio
  • 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)
  (MGI Ref ID J:76318)
  • Normal - however, the T to B cells ratio is normal
  (MGI Ref ID J:76318)

• glomerulonephritis
  • affected glomeruli are enlarged with a thickened basement membrane and contain perivascular aggregates of inflammatory infiltrate and immune complex deposition
  (MGI Ref ID J:76318)
  • elderly mice exhibit membranoproliferative glomerulonephritis that is focal and of moderate intensity
  (MGI Ref ID J:76318)

• increased inflammatory response
  • in elderly mice, increased mononuclear infiltrate is observed in the lung, kidney and liver
  (MGI Ref ID J:76318)
  • at 15 months, mice exhibit features of autoimmune disease
  (MGI Ref ID J:76318)

• abnormal T cell differentiation
  • the fraction of mature (CD4+ and, especially, CD8+) thymocytes in the thymus is increased with a decreased in immature double positive thymocytes
  (MGI Ref ID J:76318)

• enlarged spleen
  • at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice
  (MGI Ref ID J:76318)

• abnormal immune system morphology
  (MGI Ref ID J:76318)

• increased anti-double stranded DNA antibody level
  • the amount of double stranded DNA antibodies is increased relative to in wild-type mice and corresponds to the severity of organ damage
  (MGI Ref ID J:76318)

• increased memory T cell number
  • at 3 to 4 weeks and at 15 months, the number of CD44^hiCD69- memory T cells is increased
  (MGI Ref ID J:76318)

• increased susceptibility to autoimmune disorder
  • at 15 months, mice exhibit features of autoimmune disease including inflammatory infiltrate, adnormal accumulation of effector/memory T cells, and double stranded DNA antibodies
  (MGI Ref ID J:76318)

• liver inflammation
  • in elderly mice, inflammatory infiltrate accumulates in the liver and perivascular infiltrates are observed
  (MGI Ref ID J:76318)

• abnormal immune system physiology
  (MGI Ref ID J:76318)

• lung inflammation
  • in elderly mice, inflammatory infiltrate accumulates in the lung
  (MGI Ref ID J:76318)

• increased spleen weight
  • 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)
  (MGI Ref ID J:76318)

• increased T cell proliferation
  • 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
  (MGI Ref ID J:76318)
  • 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
  (MGI Ref ID J:76318)

• abnormal spleen white pulp morphology
  • at 15 months, mice display white pulp hyperplasia and increased sinusoidal cellularity
  (MGI Ref ID J:76318)

cellular phenotype

• increased T cell proliferation
  • 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
  (MGI Ref ID J:76318)
  • 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
  (MGI Ref ID J:76318)

• abnormal cell death
  • cell death induced by Myc expression in primary fibroblast cells is somewhat less efficient than in wild-type primary fibroblast
  (MGI Ref ID J:75726)

• abnormal cell physiology
  • adenovirus-Myc fails to induce S phase as it does in wild-type mouse embryonic fibroblasts
  (MGI Ref ID J:75726)

integument phenotype

• abnormal skin morphology
  • elderly mice exhibit skin wounds
  (MGI Ref ID J:76318)

• progressive hair loss
  • elderly mice exhibit considerable hair loss
  (MGI Ref ID J:76318)

• reddish skin
  • elderly mice exhibit erythema affecting the head and neck
  (MGI Ref ID J:76318)

liver/biliary system phenotype

• liver inflammation
  • in elderly mice, inflammatory infiltrate accumulates in the liver and perivascular infiltrates are observed
  (MGI Ref ID J:76318)

mortality/aging

• premature death
  • at 15 months, only 27% of mice are alive compared to 67% of wild-type mice
  (MGI Ref ID J:76318)

renal/urinary system phenotype

• renal glomerulus hypertrophy
  • affected glomeruli are enlarged
  (MGI Ref ID J:76318)

• glomerulonephritis
  • affected glomeruli are enlarged with a thickened basement membrane and contain perivascular aggregates of inflammatory infiltrate and immune complex deposition
  (MGI Ref ID J:76318)
  • elderly mice exhibit membranoproliferative glomerulonephritis that is focal and of moderate intensity
  (MGI Ref ID J:76318)

• increased renal glomerulus basement membrane thickness
  • affected glomeruli display a thickened basement membrane
  (MGI Ref ID J:76318)

• renal glomerular immunoglobulin deposits
  (MGI Ref ID J:76318)

respiratory system phenotype

• lung inflammation
  • in elderly mice, inflammatory infiltrate accumulates in the lung
  (MGI Ref ID J:76318)

growth/size/body region phenotype

• enlarged spleen
  • at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice
  (MGI Ref ID J:76318)

• increased spleen weight
  • 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)
  (MGI Ref ID J:76318)

hematopoietic system phenotype

• abnormal spleen white pulp morphology
  • at 15 months, mice display white pulp hyperplasia and increased sinusoidal cellularity
  (MGI Ref ID J:76318)

• increased memory T cell number
  • at 3 to 4 weeks and at 15 months, the number of CD44^hiCD69- memory T cells is increased
  (MGI Ref ID J:76318)

• increased T cell proliferation
  • 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
  (MGI Ref ID J:76318)
  • 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
  (MGI Ref ID J:76318)

• abnormal T cell differentiation
  • the fraction of mature (CD4+ and, especially, CD8+) thymocytes in the thymus is increased with a decreased in immature double positive thymocytes
  (MGI Ref ID J:76318)

• enlarged spleen
  • at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice
  (MGI Ref ID J:76318)

• abnormal T cell subpopulation ratio
  • 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)
  (MGI Ref ID J:76318)
  • Normal - however, the T to B cells ratio is normal
  (MGI Ref ID J:76318)

• increased spleen weight
  • 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)
  (MGI Ref ID J:76318)