Analysis Tools
mortality/aging
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• all mice die around 85 weeks of age, with a median survival of 76 weeks before complete liver failure
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liver/biliary system
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• 8 week old mice show anisokaryotic clusters resembling low-grade dysplastic nodules that develop into high-grade dysplastic nodules at 12 weeks of age that is similar to large liver dysplasia
• mice supplied with the nicotinamide riboside diet at 3 weeks of age do not show dysplastic lesions in the liver or DNA damage
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• early hepatocellular carcinoma (HCC) emerges between 24-54 weeks of age, with mice showing low-grade and differentiated HCC at 54-65 weeks and 40% of mutants developing high-grade tumors occupying 20-60% of the liver between 65-75 weeks of age
• 25-50% of hepatocytes are Ki67+, suggesting aggressive tumors
• tumors are well/moderately differentiated, with 20% glandular/acinar and 80% trabecular
• however, no cholangiocarcinoma is seen
• mice treated with doxycycline to cease URI1 expression at 8 weeks of age for 24 weeks show abolished dysplastic foci and prevention of early tumors
• mice treated with doxycycline at 8 weeks until 60 weeks of age show prevention of tumor development
• when mice are treated with doxycycline at 24 weeks (when mice have high-grade dysplastic nodules/early HCC and adenomas) for 28 weeks, only residual anisokaryotic clusters are seen and no adenomas or HCCs are detected
• however, when treatment with doxycycline begins above 60 weeks of age, HCC does not regress
• prolonged nicotinamide riboside treatment prevents tumor development
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• 8 week old mice exhibit liver fibrosis that increases over time until 24 weeks
• mice treated with doxycycline to cease URI1 expression at 8 weeks of age for 24 weeks show reduced liver fibrosis
• mice supplied with the nicotinamide riboside diet at 3 weeks of age have reduced liver fibrosis
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neoplasm
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• diethylnitrosamine (DEN)-treated mice develop HCC at 30 weeks of age
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• early hepatocellular carcinoma (HCC) emerges between 24-54 weeks of age, with mice showing low-grade and differentiated HCC at 54-65 weeks and 40% of mutants developing high-grade tumors occupying 20-60% of the liver between 65-75 weeks of age
• 25-50% of hepatocytes are Ki67+, suggesting aggressive tumors
• tumors are well/moderately differentiated, with 20% glandular/acinar and 80% trabecular
• however, no cholangiocarcinoma is seen
• mice treated with doxycycline to cease URI1 expression at 8 weeks of age for 24 weeks show abolished dysplastic foci and prevention of early tumors
• mice treated with doxycycline at 8 weeks until 60 weeks of age show prevention of tumor development
• when mice are treated with doxycycline at 24 weeks (when mice have high-grade dysplastic nodules/early HCC and adenomas) for 28 weeks, only residual anisokaryotic clusters are seen and no adenomas or HCCs are detected
• however, when treatment with doxycycline begins above 60 weeks of age, HCC does not regress
• prolonged nicotinamide riboside treatment prevents tumor development
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• metastases into lungs are seen
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homeostasis/metabolism
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• serum glucose levels are decreased in 65 week old mice
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• serum albumin is increased in 65 week old mice
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• NAD+ concentrations are reduced in 3- and 6-week old livers
• mice supplied with a nicotinamide riboside (NR) diet at 3 weeks of age show increased hepatic NAD+ concentrations
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• alanine transaminase (ALT) levels are increased in 65 week old mice
• however, serum ALT levels are unchanged in 8 week old mice
• mice treated with doxycycline at 8 weeks until 60 weeks of age show normalization of ALT levels
• prolonged nicotinamide riboside treatment reduces ALT levels
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• total bile acids are increased in 65 week old mice
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• diethylnitrosamine (DEN)-treated mice develop HCC at 30 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:217463 | |
