Analysis Tools
mortality/aging
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• mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice
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• many mice die from thymic lymphoma; none survived greater than 4.5 months of age without a thymic lymphoma
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growth/size/body
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• homozygotes appear smaller at birth
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• female and male homozygotes weigh less that control littermates from P8 to 3 months of age
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immune system
| N |
• no abnormalities in B lymphocytes, granulocytes or myeloid cells observed
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• thymic lymphomas are highly metastatic and consist of immature T cells
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• increased number of immature double positive cells
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• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes
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• 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
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• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present
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reproductive system
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• absence of primordial and mature ovarian follicles
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small ovary
(
J:34193
)
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• no proliferation or degeneration in as part of the estrous cycle
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• complete absence of mature gametes
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azoospermia
(
J:34193
)
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• absence of mature sperm
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• reduced number of cells
• degeneration of cells evident
• some barren of all cells except Sertoli cells
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small testis
(
J:34193
)
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absent estrus
(
J:34193
)
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• females never enter estrous
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• females never exhibit copulation plugs
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• normal mating behavior evident by the presence of copulation plugs in control females; however, pregnancy never results
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neoplasm
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• thymic lymphomas are highly metastatic and consist of immature T cells
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cellular
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• complete absence of mature gametes
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azoospermia
(
J:34193
)
|
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• absence of mature sperm
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• 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
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• 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
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• mutant fibroblasts grew more slowly in culture than control cells
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• 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)
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behavior/neurological
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• 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
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• in addition, the maximum difference in stride lengths was greater in mutant mice, suggestive of ataxia
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• mutant mice reared less often than controls
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• reduced horizontal activity was shown by reduced movement around an open field
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nervous system
| N |
• no defects in brain architecture
• no evidence of neurodegeneration
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• heme oxygenase 1 is increase in Purkinje cells, indicating oxidative damage particularly in these cells
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hematopoietic system
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• thymic lymphomas are highly metastatic and consist of immature T cells
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• increased number of immature double positive cells
|
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• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes
|
|
• 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
|
|
• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present
|
endocrine/exocrine glands
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• thymic lymphomas are highly metastatic and consist of immature T cells
|
|
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• absence of primordial and mature ovarian follicles
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small ovary
(
J:34193
)
|
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• reduced number of cells
• degeneration of cells evident
• some barren of all cells except Sertoli cells
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small testis
(
J:34193
)
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homeostasis/metabolism
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• mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ataxia telangiectasia | DOID:12704 |
OMIM:208900 |
J:34193 , J:57115 | |
