mortality/aging
• embryonic lethality between E13.5 and E16.5, with 25% dead at E14.5 and 60% at E15.5; no live embryos are recovered after E15.5
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cardiovascular system
• exhibit an approximate 33% reduction in mean cell size in the heart
• exhibit significantly increased apoptosis in the heart at E14.5 but not at E12.5
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• sparsely cellular myocardium
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• the thin myocardial wall is composed of wisps of thin trabecular myocardium
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• heart ventricular wall has lost the normal trabecular and external compact myocytes
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• in the most severely affected mutants, the myocardium is composed almost entirely of the trabecular layer with no appreciable compact layer beneath the epicardium
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• wall is thinner and contains fewer myocytes
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• exhibit multifocal variable sized hemorrhages in between the hepatic cords
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liver/biliary system
• exhibit multifocal variable sized hemorrhages in between the hepatic cords
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• exhibit significantly increased apoptosis in the liver at E14.5 and E15.5, predominantly in hepatocytes
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• majority of E14.5 and E15.5 embryos exhibit liver lesions characterized by loosely arranged hepatocytes mixed with numerous red blood cells
• exhibit an approximate 25% reduction in mean cell size in the liver
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• many hepatocyes have condensed nuclei (karyopyknosis), fragmented nuclei (karyorrhexis) or lost their nuclei (karyolysis)
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• liver shows loss of hepatocytes
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• exhibit liver lesions characterized by hepatocytes that are separated from each other
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homeostasis/metabolism
cellular
• MEFs exhibit decreased cell size compared to wild-type
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• although MEFs under normal culture conditions do not show increased apoptosis, they do show increased susceptibility to TNFalpha-induced apoptosis
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• exhibit significantly increased apoptosis in the liver at E14.5 and E15.5, predominantly in hepatocytes
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muscle
• sparsely cellular myocardium
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• the thin myocardial wall is composed of wisps of thin trabecular myocardium
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• heart ventricular wall has lost the normal trabecular and external compact myocytes
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• in the most severely affected mutants, the myocardium is composed almost entirely of the trabecular layer with no appreciable compact layer beneath the epicardium
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integument
• about 20% of embryos are pale at E13.5 and by E14.5 and E15.5, majority of embryos are pale
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