liver/biliary system
N |
• under specific pathogen-free conditions, homozygotes survive beyond 16 months of age with no alterations in liver histology or baseline liver function
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• at 24 h post tunicamycin treatment, mice fail to exhibit any significant hepatosteatosis, unlike similarly treated wild-type and heterozygous controls
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• when fed a high fat diet for 10 weeks, mice exhibit less pale and buoyant livers with significantly decreased accumulation of lipid droplets in hepatocytes relative to similarly fed heterozygous controls
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cellular
• following treatment with UPR inducers (tunicamycin or thapsigargin), isolated hepatocytes exhibit significantly less endoplasmic reticulum (ER) stress-induced death than similarly treated wild-type or heterozygous hepatocytes, as determined by a cell viability assay
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• at 24 h post treatment with the unfolded protein response (UPR) inducer tunicamycin, no CHOP induction is observed in liver and kidney tissues, unlike in wild-type and heterozygous controls
• at 16 h post treatment with tunicamycin or thapsigargin, isolated hepatocytes exhibit significantly reduced levels of ER stress and UPR-associated proteins relative to similarly treated wild-type and heterozygous hepatocytes
• when fed a high fat diet for 10 weeks, mice show a severe reduction of UPR marker induction in liver lysates relative to similarly fed heterozygous controls
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growth/size/body
• when fed a high fat diet for 10 weeks, mice gain significantly less body weight than similarly fed heterozygous controls
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• at baseline, homozygotes are slightly but consistently smaller than wild-type or heterozygous controls
• however, no developmental defects are observed
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homeostasis/metabolism
• when fed a high fat diet for 10 weeks, mice gain significantly less body weight than similarly fed heterozygous controls
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• when fed a high fat diet for 10 weeks, mice exhibit significantly lower serum triglyceride levels than similarly fed heterozygous controls
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• at 24 h post tunicamycin treatment, mice exhibit significantly lower serum alanine aminotransferase (ALT) levels than similarly treated heterozygous controls
• when fed a high fat diet for 10 weeks, mice exhibit significantly lower serum ALT levels than similarly fed heterozygous controls
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• at 24 h post tunicamycin treatment, mice fail to exhibit any significant weight loss, liver damage or hepatosteatosis and show a smaller increase in serum alanine aminotransferase (ALT) levels relative to similarly treated heterozygous controls
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