liver/biliary system
• 3-month-old mice exhibit liver overgrowth
• however, liver does not show alterations in canalicular morphology, hepatocyte ultrastructure, or hepatic plate thickness, indicating normal hepatocyte polarity
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• 3-month-old mice exhibit increased liver weight relative to total body weight, which is increased in 6-month-old mice and is about 5-fold higher than in controls at 12 months of age
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• liver shows malformation of the portal triads with an increase of ductal structures
• liver shows massive enrichment of small cells at portal triads
• however, the arrangement of hepatic cells close to the central vein appears normal
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• 12-month-old mice exhibit numerous liver tumors that have characteristics of both hepatocellular carcinoma and cholangiocarcinoma, possibly representing an intermediate tumor phenotype
• tumors show cells with enlarged, atypical nuclei and irregular arrangements of hepatocytes, and the border between each tumor and normal liver tissue is made up of a collagen-rich capsule
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• liver shows the presence of fibrotic areas close to portal triads and in the periportal zones
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• 6-month-old livers show enhanced proliferation of immature biliary epithelial cell-like progenitor cells
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• livers show an enrichment of activated myofibroblasts and infiltration with inflammatory macrophages
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neoplasm
• 12-month-old mice exhibit numerous liver tumors that have characteristics of both hepatocellular carcinoma and cholangiocarcinoma, possibly representing an intermediate tumor phenotype
• tumors show cells with enlarged, atypical nuclei and irregular arrangements of hepatocytes, and the border between each tumor and normal liver tissue is made up of a collagen-rich capsule
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growth/size/body
• 3-month-old mice exhibit increased liver weight relative to total body weight, which is increased in 6-month-old mice and is about 5-fold higher than in controls at 12 months of age
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immune system
• livers show an enrichment of activated myofibroblasts and infiltration with inflammatory macrophages
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