Analysis Tools
mortality/aging
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• after whole body gamma-irradiation with 7 Gy, all 4-6-week-old homozygotes die between 9 and 15 days post-irradiation relative to only 16% of control littermates
• in contrast, homozygotes remain viable after exposure to lower doses of gamma-irradiation (1.5 Gy)
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growth/size/body
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• on average, male and female homozygotes weigh 25% and 15% less, respectively, than their wild-type littermates
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hematopoietic system
small thymus
(
J:83164
)
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• at 8 weeks of age, mutant thymuses are significantly smaller than wild-type
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• at 8 weeks of age, mutant thymuses contain fewer cells than those of wild-type littermates
• however, the lymphoid organ architecture of mutant thymuses appears normal, as determined by H&E staining
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• at 8 weeks of age, homozygotes show aberrant progression out of the CD44_CD25+ stage , suggesting impaired early thymocyte development
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• at 8 weeks of age, homozygotes show a deficiency of mature B cells (IgMloIgDhi) in the spleen, suggesting improper B lymphocyte development
• however, no significant differences are observed in bone marrow pro-B, pre-B, myeloid, and erythroid progenitor populations relative to wild-type mice
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• at 8 weeks of age, homozygotes display a reduced T cell count relative to wild-type littermates
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immune system
small thymus
(
J:83164
)
|
• at 8 weeks of age, mutant thymuses are significantly smaller than wild-type
|
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• at 8 weeks of age, mutant thymuses contain fewer cells than those of wild-type littermates
• however, the lymphoid organ architecture of mutant thymuses appears normal, as determined by H&E staining
|
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• at 8 weeks of age, homozygotes show aberrant progression out of the CD44_CD25+ stage , suggesting impaired early thymocyte development
|
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• at 8 weeks of age, homozygotes show a deficiency of mature B cells (IgMloIgDhi) in the spleen, suggesting improper B lymphocyte development
• however, no significant differences are observed in bone marrow pro-B, pre-B, myeloid, and erythroid progenitor populations relative to wild-type mice
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• at 8 weeks of age, homozygotes display a reduced T cell count relative to wild-type littermates
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cellular
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• mutant MEFs proliferate more slowly than wild-type MEFs and display absence of detectable, irradiation-induced nuclear foci, suggesting that the truncated protein cannot fully perform its functions as a DNA damage-response element
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• MEFs derived from homozygous mutant mice exhibit chromosomal abnormalities consistent with defects in DNA repair
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• after exposure to gamma-irradiation, mutant MEFs (passage 2) exhibit a ~2-fold increase in levels of chromatid breaks and gaps relative to wild-type MEFs
• although mutant MEFs display relatively high chromatid exchange rates at 0.5 Gy relative to wild-type MEFs, this difference is less evident at 1.5 Gy, possibly due to limited progression to mitosis of the most damaged cells from both populations during this time frame
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• untreated MEFs (passage 2) derived from mutant mice display increased levels of chromatid gaps, breaks, and, to a lesser extent, exchanges relative to untreated wild-type MEFs, suggesting an intrinsic genomic stability defect in mutant cells
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reproductive system
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• homozygotes are fertile; however, intercrosses between homozygous mutant mice produce small litters
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homeostasis/metabolism
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• after whole body gamma-irradiation with 7 Gy, all 4-6-week-old homozygotes die between 9 and 15 days post-irradiation relative to only 16% of control littermates
• in contrast, homozygotes remain viable after exposure to lower doses of gamma-irradiation (1.5 Gy)
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endocrine/exocrine glands
small thymus
(
J:83164
)
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• at 8 weeks of age, mutant thymuses are significantly smaller than wild-type
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• at 8 weeks of age, mutant thymuses contain fewer cells than those of wild-type littermates
• however, the lymphoid organ architecture of mutant thymuses appears normal, as determined by H&E staining
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