Analysis Tools
homeostasis/metabolism
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• after 8 months of diethylnitrosamine (DEN) treatment, heterozygotes show an intermediate increase in serum ALT activity compared to DEN-treated homozygous mutant mice and wild-type controls
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• in culture, primary hepatocytes isolated from heterozygous mutant mice clear [13C]ACE more slowly than those of wild-type controls
• after exposure to low-dose ethanol (2 g/kg), heterozygotes display slower ACE clearance but no behavioral abnormality compared to wild-type controls
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• after 8 months of DEN treatment, heterozygotes show an intermediate increase in the total number and volume of hepatocellular carcinomas compared to DEN-treated homozygous mutant mice and wild-type controls
• liver histology indicates increased focal hepatic lesions while phospho-H2AX staining shows a higher degree of DNA damage relative to DEN-treated wild-type controls
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behavior/neurological
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• after 4 g/kg ethanol challenge, heterozygotes show an intermediate increase in behavioral scores including mild ataxia compared to homozygous mutant mice and wild-type controls
• after 8 g/kg ethanol challenge, heterozygotes display more severe behavioral abnormalities including loss of righting reflex, similar to homozygous mutant mice
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mortality/aging
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• after acute ethanol challenge with 8 g/kg (lethal dose), but not 2 or 4 g/kg, heterozygotes show an intermediate reduction in survival rate compared to homozygous mutant mice and wild-type controls
• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes display reduced survival starting at 2 weeks, unlike wild-type controls
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growth/size/body
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• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes show an intermediate reduction in body weight compared to homozygous mutant mice and wild-type controls
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cellular
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• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes display a moderate increase in hepatocyte apoptosis, as shown by histology and cleaved caspase 3 staining
• however, no inflammatory or necrotic changes are observed in the esophagus or stomach after chronic ethanol challenge
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hematopoietic system
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• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes show an intermediate reduction in white cell count compared to homozygous mutant mice and wild-type controls
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liver/biliary system
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• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes display a moderate increase in hepatocyte apoptosis, as shown by histology and cleaved caspase 3 staining
• however, no inflammatory or necrotic changes are observed in the esophagus or stomach after chronic ethanol challenge
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neoplasm
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• after 8 months of DEN treatment, heterozygotes show an intermediate increase in the total number and volume of hepatocellular carcinomas compared to DEN-treated homozygous mutant mice and wild-type controls
• liver histology indicates increased focal hepatic lesions while phospho-H2AX staining shows a higher degree of DNA damage relative to DEN-treated wild-type controls
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immune system
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• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes show an intermediate reduction in white cell count compared to homozygous mutant mice and wild-type controls
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pigmentation
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• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, heterozygotes display enhanced pigmentation of paw skin, unlike wild-type controls
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