Phenotypes for Atm MGI:2175703 MGI Mouse

increased mortality induced by gamma-irradiation ( J:34193 )

• mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice

premature death ( J:34193 )

• many mice die from thymic lymphoma; none survived greater than 4.5 months of age without a thymic lymphoma

decreased body size ( J:34193 )

• homozygotes appear smaller at birth

decreased body weight ( J:34193 )

• female and male homozygotes weigh less that control littermates from P8 to 3 months of age

immune system phenotype ( J:34193 )

N	• no abnormalities in B lymphocytes, granulocytes or myeloid cells observed

increased double-positive T cell number ( J:34193 )

• increased number of immature double positive cells

decreased T cell number ( J:34193 )

• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes

decreased double-positive T cell number ( J:34193 )

• 59% reduction in Cd3/Cd4 double positive T lymphocytes

• 67% reduction in Cd3/Cd8 double positive T lymphocytes

• reduction in Cd5, Cd4, and Cd8 positive T lymphocytes

decreased activated T cell number ( J:34193 )

• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present

abnormal female reproductive system morphology ( J:34193 )

absent ovarian follicles ( J:34193 )

• absence of primordial and mature ovarian follicles

small ovary ( J:34193 )

abnormal uterus morphology ( J:34193 )

• no proliferation or degeneration in as part of the estrous cycle

abnormal gametogenesis ( J:34193 )

absent oocytes ( J:34193 )

• complete absence of mature gametes

azoospermia ( J:34193 )

• absence of mature sperm

arrest of spermatogenesis ( J:34193 )

abnormal male reproductive system morphology ( J:34193 )

abnormal seminiferous tubule morphology ( J:34193 )

• reduced number of cells

• degeneration of cells evident

• some barren of all cells except Sertoli cells

small testis ( J:34193 )

abnormal reproductive system physiology ( J:34193 )

absent estrus ( J:34193 )

• females never enter estrous

absent estrous cycle ( J:34193 )

female infertility ( J:34193 )

• females never exhibit copulation plugs

male infertility ( J:34193 )

• normal mating behavior evident by the presence of copulation plugs in control females; however, pregnancy never results

increased T cell derived lymphoma incidence ( J:34193 )

• thymic lymphomas are highly metastatic and consist of immature T cells

absent oocytes ( J:34193 )

• complete absence of mature gametes

azoospermia ( J:34193 )

• absence of mature sperm

abnormal lysosome morphology ( J:59933 )

• significant increase in the number of lysosomes in cerebellar Purkinje cells and in pyramidal cells of the hippocampus in the absence of any neuronal degeneration at 4-12 weeks of age, before the onset of T cell lymphoma

abnormal cell cycle ( J:34193 )

increased cellular sensitivity to gamma-irradiation ( J:34193 )

• mutant fibroblasts show increased radioresistant DNA synthesis (RDS) after 5 to 15 Gy of gamma-irradiation compared to controls, indicating that cell cycle checkpoints are abnormal

decreased fibroblast proliferation ( J:34193 )

• mutant fibroblasts grew more slowly in culture than control cells

oxidative stress ( J:57115 )

• tissues from mutants are under oxidative stress and suffer oxidative damage, especially in the brain

• oxidative damage to proteins and lipids as indicated by elevated nitrotyrosine levels in the brain (but not the liver) and elevated F2-isoprostanes in the testes (indicative of lipid damage)

• activity of the isozyme, heme oxygenase, is increased 600% in the cerebellum (but not in the cortex)

impaired coordination ( J:34193 )

• mutant mice were not able to stay on a rota-rod as long as controls

• impaired performance was not due to decreased strength since mice were able to suspend from a wire lid as long as controls

short stride length ( J:34193 )

• in addition, the maximum difference in stride lengths was greater in mutant mice, suggestive of ataxia

decreased vertical activity ( J:34193 )

• mutant mice reared less often than controls

decreased locomotor activity ( J:34193 )

• reduced horizontal activity was shown by reduced movement around an open field

nervous system phenotype ( J:34193 )

N	• no defects in brain architecture • no evidence of neurodegeneration

abnormal Purkinje cell morphology ( J:57115 )

• heme oxygenase 1 is increase in Purkinje cells, indicating oxidative damage particularly in these cells