Mouse Genome Informatics
hm1
    Sirt3tm1.1Fwa/Sirt3tm1.1Fwa
involves: 129/Sv * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice are phenotypically normal with unremarkable metabolism and adaptive thermogenesis


Mouse Genome Informatics
hm2
    Sirt3tm1.1Fwa/Sirt3tm1.1Fwa
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• increase in weight is due to increased adiposity

growth/size/body
• increase in weight is due to increased adiposity
• mutants on a high-fat diet develop diet induced obesity at an accelerated rate compared to controls
• on a high-fat diet, mutants weight 7% more than wild-type mice by 18 weeks, 10% more by 33 weeks, and 15% more by 52 weeks

homeostasis/metabolism
• mutants on a high-fat diet develop diet induced obesity at an accelerated rate compared to controls
• on a high-fat diet, mutants weight 7% more than wild-type mice by 18 weeks, 10% more by 33 weeks, and 15% more by 52 weeks
• obese mutants fed a high-fat diet exhibit hyperglycemia during glucose-tolerance testing
• non-obese mutants fed a standard diet show marked hyperglycemia upon intraperitoneal glucose injection
• 12 month old mutants on a high-fat diet show a 285% increase in fasting insulin levels compared to wild-type mice
• however, leptin, adiponectin, and resistin are unchanged
• mutants fed a standard diet exhibit a 53% reduction in LCAD enzymatic activity mutants fed a standard diet exhibit a 53% reduction in long-chain acyl-CoA dehydrogenase (LCAD) enzymatic activity
• CO2 exhalation is 15% lower in mutants during light and 16% during dark cycles
• however, no differences in respiratory exchange ratio are seen
• oxygen consumption is 15% lower in mutants during light and 14% lower during dark cycles
• obese mutants fed a high-fat diet show insulin resistance in insulin tolerance testing
• non-obese mutants fed a standard diet show marked insulin resistance upon intraperitoneal insulin injection
• 12 month old mutants on a high-fat diet show a 141% increase in cholesterol levels compared to wild-type mice
• 12 month old mutants on a high-fat diet show a 60% increase in low-density lipoproteins compared to wild-type mice
• 12 month old mutants on a high-fat diet show a 100% increase in very-low-density lipoproteins compared to wild-type mice
• 12 month old mutants on a high-fat diet show a 97% increase in trigylcerides compared to wild-type mice
• 3 month old mutants fed a high-fat diet have 41% more hepatic cholesterol esters
• 3 month old mutants fed a high-fat diet have 38% more hepatic trigylcerides than wild-type mice
• aged obese mutants fed a high-fat diet exhibit higher serum levels of inflammatory cytokines, but are unchanged in nonobese 3-month old mutants
• aged obese mutants fed a high-fat diet exhibit 3-fold higher interferon-gamma levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 3-fold higher IL-10 levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 12-fold higher IL-12p70 levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 10-fold higher IL-6 levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 1.7-fold higher TNF-alpha levels than wild-type mice

immune system
• aged obese mutants fed a high-fat diet exhibit higher serum levels of inflammatory cytokines, but are unchanged in nonobese 3-month old mutants
• aged obese mutants fed a high-fat diet exhibit 3-fold higher interferon-gamma levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 3-fold higher IL-10 levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 12-fold higher IL-12p70 levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 10-fold higher IL-6 levels than wild-type mice
• aged obese mutants fed a high-fat diet exhibit 1.7-fold higher TNF-alpha levels than wild-type mice
• aged mutants fed a high-fat diet exhibit more lobular lymphoplasmacytic inflammation, and more hepatocyte ballooning degeneration compared to wild-type mice

liver/biliary system
• 3 month old mutants fed a high-fat diet have 41% more hepatic cholesterol esters
• 3 month old mutants fed a high-fat diet have 38% more hepatic trigylcerides than wild-type mice
• aged mutants fed a high-fat diet exhibit more lobular lymphoplasmacytic inflammation, and more hepatocyte ballooning degeneration compared to wild-type mice
• mutants fed a high-fat diet show higher lipid levels in the liver than in controls fed a high-fat diet
• mutants fed a high-fat diet show an increased accumulation of hepatic long-chain acylcarnitine species, but not organic acids or amino acids
• aged mutants fed a high-fat diet exhibit more macrovesicular steatosis
• aged mutants fed a high-fat diet exhibit more hepatic fibrosis compared to wild-type mice


Mouse Genome Informatics
cx3
    Scd1tm1Ntam/Scd1tm1Ntam
Sirt3tm1.1Fwa/Sirt3tm1.1Fwa

involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• double mutants fed a high-fat diet exhibit improved insulin sensitivity compared to single Sirt3 homozygotes
• double mutants fed a high-fat diet exhibit reduced hepatic triglycerides when compared to single Sirt3 homozygotes
• however, mutant do not exhibit any differences from wild-type mice in hepatic lipids when fed a standard diet