Analysis Tools
mortality/aging
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• mutants show increased sensitivity to PMEA (a nucleotide analog); minimal toxic dose (0.5 mg/kg) is 5-fold lower than that of wild-type (2.5 mg/kg) and at dose of 2 mg/kg all mutants die, whereas wild-type all survive
• LD50 is half of the LD50 for wild-type mice
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growth/size/body
weight loss
(
J:117326
)
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• after PMEA treatment (2 mg/kg), mutants show weight loss as early as 24 hours after treatment, and by day 5 have lost >20% body weight whereas wild-type mice have lost <5% body weight by this time
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homeostasis/metabolism
digestive/alimentary system
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• epithelium of forestomach is damaged by acute mucositis, leaving horny layer and denuded subepithelial tissue after PMEA treatment
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• villi are decreased in size in mice after PMEA treatment
• basal portions of glands are dilated
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• denuded subepithelial tissue shows edema and inflammatory cell infiltrate
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• mutants display severe atrophic toxic colitis after PMEA treatment, with loss of glands, decreased submucosal thickness, and inflammatory infiltrates; microcysts are also present
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• there are prominent inflammatory infiltrates in submucosa after PMEA treatment
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hematopoietic system
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• almost complete lymphoid depopulation in cortical region of thymus is observed in mutant thymus after PMEA treatment
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• erythroid and myeloid populations in red pulp are decreased, and replaced with stromal cells after PMEA treatment
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small spleen
(
J:117326
)
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• after PMEA treatment, spleens are smaller in mutants
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• lymphoid follicles are reduced in number and size
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immune system
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• denuded subepithelial tissue shows edema and inflammatory cell infiltrate
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• mutants display severe atrophic toxic colitis after PMEA treatment, with loss of glands, decreased submucosal thickness, and inflammatory infiltrates; microcysts are also present
|
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• there are prominent inflammatory infiltrates in submucosa after PMEA treatment
|
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• almost complete lymphoid depopulation in cortical region of thymus is observed in mutant thymus after PMEA treatment
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• erythroid and myeloid populations in red pulp are decreased, and replaced with stromal cells after PMEA treatment
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small spleen
(
J:117326
)
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• after PMEA treatment, spleens are smaller in mutants
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• lymphoid follicles are reduced in number and size
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cardiovascular system
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• mutants have 1.8-fold higher brain/plasma ratios of PMEA compared to wild-type
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nervous system
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• mutants have 1.8-fold higher brain/plasma ratios of PMEA compared to wild-type
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endocrine/exocrine glands
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• almost complete lymphoid depopulation in cortical region of thymus is observed in mutant thymus after PMEA treatment
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