mortality/aging
• prior to E12.5, homozygotes appear morphologically normal; however, mutant embryos die progressively from E12.5 to E14 as a result of massive liver degeneration
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liver/biliary system
• dead or moribund mutant embryos exhibit massive liver hemorrhage
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• at E13, homozygotes exhibit extensive hepatocyte apoptosis, as shown by TUNEL assays
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• at E13, mutant hepatocytes appear dissociated and dying, as evidenced by the presence of pyknotic nuclei; however, fetal liver hematopoeisis appears unaffected
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small liver
(
J:54323
)
• at E13 and E13.5, surviving homozygotes are of normal body size and morphology but exhibit smaller and darker livers than wild-type mice
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• dead or moribund mutant embryos exhibit massive liver degeneration
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cardiovascular system
• dead or moribund mutant embryos exhibit massive liver hemorrhage
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cellular
• mutant MEFs exhibit significantly reduced NF-kappaB activation upon induction with TNF or IL-1alpha
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• mutant MEFs exhibit increased sensitivity to TNF-induced apoptosis relative to wild-type or heterozygous MEFs
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• at E13, homozygotes exhibit extensive hepatocyte apoptosis, as shown by TUNEL assays
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