homeostasis/metabolism
• homozygotes exhibit a 25-90% increase in glutathione (GSH) levels in most tissues, including breast, heart, lung, kidney, muscle, colon, testes, ovary, bone marrow cells, blood mononuclear leukocytes, and blood erythrocytes, but NOT in liver or small intestine
• notably, no increase in the activity of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for GSH synthesis, is observed in any of the tissues analyzed
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• homozygotes exhibit a 2-fold increase in sensitivity to etoposide phosphate, associated with higher bone marrow toxicity relative to wild-type mice
• in contrast, no significant differences in acute sodium arsenite toxicity or acute cisplatin toxicity are observed
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hematopoietic system
N |
• homozygotes are viable at least up to 4 months and display normal fertility, growth, behavior, and tissue/organ morphology, with no significant differences in hematological parameters relative to wild-type mice
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