Mouse Genome Informatics
hm
    Atmtm1Awb/Atmtm1Awb
either: 129S6/SvEvTac-Atmtm1Awb or (involves: 129S6/SvEvTac * NIH Black Swiss)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Oxidated stress in the brain of Atmtm1Awb/Atmtm1Awb mice indicated by increased levels of heme oxygenase

mortality/aging
• mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice
• many mice die from thymic lymphoma; none survived greater than 4.5 months of age without a thymic lymphoma

growth/size
• homozygotes appear smaller at birth
• female and male homozygotes weigh less that control littermates from P8 to 3 months of age

immune system
N
• no abnormalities in B lymphocytes, granulocytes or myeloid cells observed (J:34193)
• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes
• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present
• 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
• increased number of immature double positive cells

reproductive system
• absence of primordial and mature ovarian follicles (J:34193)
(J:34193)
• no proliferation or degeneration in as part of the estrous cycle (J:34193)
• complete absence of mature gametes (J:34193)
• absence of mature sperm (J:34193)
• reduced number of cells (J:34193)
• degeneration of cells evident (J:34193)
• some barren of all cells except Sertoli cells (J:34193)
(J:34193)
• females never enter estrous (J:34193)
• females never exhibit copulation plugs (J:34193)
• normal mating behavior evident by the presence of copulation plugs in control females; however, pregnancy never results (J:34193)

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

cellular
• 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
• 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
• mutant fibroblasts grew more slowly in culture than control cells
• 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)

behavior/neurological
• 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
• mutant mice reared less often than controls
• reduced horizontal activity was shown by reduced movement around an open field
• in addition, the maximum difference in stride lengths was greater in mutant mice, suggestive of ataxia

nervous system
N
• no defects in brain architecture (J:34193)
• no evidence of neurodegeneration (J:34193)
• heme oxygenase 1 is increase in Purkinje cells, indicating oxidative damage particularly in these cells

hematopoietic system
• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes
• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present
• 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
• increased number of immature double positive cells

endocrine/exocrine glands
• absence of primordial and mature ovarian follicles (J:34193)
(J:34193)
• reduced number of cells (J:34193)
• degeneration of cells evident (J:34193)
• some barren of all cells except Sertoli cells (J:34193)
(J:34193)

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

Mouse Models of Human Disease
OMIM IDRef(s)
Ataxia-Telangiectasia; AT 208900 J:34193 , J:57115