Analysis Tools
liver/biliary system
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• increase in hepatocyte apoptosis, particularly at 5 weeks
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• 5-week-old mice show an increase in hepatocyte proliferation
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• livers show inflammatory cell infiltration
• expansion of liver macrophages
• elevation of intrahepatic IL-1beta, IL-6, and TNF-alpha levels
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• 12-month old mice show signs of liver disease, including fatty change, necrosis, inflammatory cell infiltration, and increased liver injury with impaired liver damage response
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• ratio of liver weight to body weight is slightly increased in 5-week-old mice
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• hepatocytes show aberrant chromosome polyploidy during postnatal liver development
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• primary hepatocytes show higher proportions of octoploid hepatocytes but almost no diploid hepatocytes after weaning compared to wild-type hepatocytes which show increased tetraploid and octoploid and lower diploid after weaning, indicating an increase of the hepatic polyploidy population
• the proportion of octoploid hepatocytes gradually increase with age to reach almost 60% at 10 weeks whereas fewer than 20% of octoploid hepatocytes are seen in wild-type mice at the same age
• however, hepatocytes are composed of predominately diploid, with some tetraploid, before weaning as in wild-type hepatocytes and primary mouse embryonic fibroblasts exhibit normal diploidy
• livers show a decrease in the proportion of binucleated hepatocytes starting at 5 weeks of age
• -livers show an increase in the size of mononuclear hepatocytes at 10 weeks of age
• livers show cytomegalic hepatocytes and cytoplasmic vacuolization
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• livers show an increase in nuclear diameters of mononuclear hepatocytes at 10 weeks of age
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• increase in the appearance and expansion of activated hepatic stellate cells
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• livers show extensive steatosis, with increased lipid deposition in the hepatocytes and hepatocyte ballooning, characteristic of nonalcoholic steatohepatitis
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• fibrillar collagen initially seen around the portal veins gradually increases such that many livers are fibrotic at 5 and 10 weeks of age
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cellular
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• livers show an increase in nuclear diameters of mononuclear hepatocytes at 10 weeks of age
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• increase in hepatocyte apoptosis, particularly at 5 weeks
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• 5-week-old mice show an increase in hepatocyte proliferation
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growth/size/body
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• ratio of liver weight to body weight is slightly increased in 5-week-old mice
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homeostasis/metabolism
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• alanine aminotransferase (ALT) levels are highly elevated after weaning (5, 10, 20, and 52 weeks of age) but not at 3 weeks of age
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• aspartate aminotransferase (AST) levels are highly elevated after weaning but not at 3 weeks of age
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• mice show increased susceptibility to carbon tetracholoride-induced liver damage, showing more severe liver necrosis and fibrosis and higher ALT, AST, and apoptosis levels, and elevation of intrahepatic fibrogenic cytokines such as IL-6 and TNF-alpha
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immune system
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• livers show inflammatory cell infiltration
• expansion of liver macrophages
• elevation of intrahepatic IL-1beta, IL-6, and TNF-alpha levels
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neoplasm
