Phenotypes Associated with This Genotype

Genotype
MGI:5311115

• Allelic Composition: Sirt3^tm1.1Fwa/Sirt3^tm1.1Fwa
• Genetic Background: involves: 129S6/SvEvTac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

adipose tissue

increased total body fat amount ( J:178653 )

• increase in weight is due to increased adiposity

growth/size/body

increased susceptibility to diet-induced obesity ( J:178653 )

• 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

increased susceptibility to diet-induced obesity ( J:178653 )

• 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

hyperglycemia ( J:178653 )

• 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

increased circulating insulin level ( J:178653 )

• 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

abnormal enzyme/coenzyme level ( J:178653 )

• 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

decreased carbon dioxide production ( J:178653 )

• CO2 exhalation is 15% lower in mutants during light and 16% during dark cycles

• however, no differences in respiratory exchange ratio are seen

decreased oxygen consumption ( J:178653 )

• oxygen consumption is 15% lower in mutants during light and 14% lower during dark cycles

insulin resistance ( J:178653 )

• 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

abnormal lipid homeostasis ( J:178653 )

increased circulating cholesterol level ( J:178653 )

• 12 month old mutants on a high-fat diet show a 141% increase in cholesterol levels compared to wild-type mice

increased circulating LDL cholesterol level ( J:178653 )

• 12 month old mutants on a high-fat diet show a 60% increase in low-density lipoproteins compared to wild-type mice

increased circulating VLDL cholesterol level ( J:178653 )

• 12 month old mutants on a high-fat diet show a 100% increase in very-low-density lipoproteins compared to wild-type mice

increased circulating triglyceride level ( J:178653 )

• 12 month old mutants on a high-fat diet show a 97% increase in trigylcerides compared to wild-type mice

increased liver cholesterol level ( J:178653 )

• 3 month old mutants fed a high-fat diet have 41% more hepatic cholesterol esters

increased liver triglyceride level ( J:178653 )

• 3 month old mutants fed a high-fat diet have 38% more hepatic trigylcerides than wild-type mice

abnormal cytokine level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit higher serum levels of inflammatory cytokines, but are unchanged in nonobese 3-month old mutants

increased circulating interferon-gamma level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 3-fold higher interferon-gamma levels than wild-type mice

increased circulating interleukin-10 level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 3-fold higher IL-10 levels than wild-type mice

increased circulating interleukin-12 level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 12-fold higher IL-12p70 levels than wild-type mice

increased circulating interleukin-6 level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 10-fold higher IL-6 levels than wild-type mice

increased circulating tumor necrosis factor level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 1.7-fold higher TNF-alpha levels than wild-type mice

immune system

abnormal cytokine level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit higher serum levels of inflammatory cytokines, but are unchanged in nonobese 3-month old mutants

increased circulating interferon-gamma level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 3-fold higher interferon-gamma levels than wild-type mice

increased circulating interleukin-10 level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 3-fold higher IL-10 levels than wild-type mice

increased circulating interleukin-12 level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 12-fold higher IL-12p70 levels than wild-type mice

increased circulating interleukin-6 level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 10-fold higher IL-6 levels than wild-type mice

increased circulating tumor necrosis factor level ( J:178653 )

• aged obese mutants fed a high-fat diet exhibit 1.7-fold higher TNF-alpha levels than wild-type mice

liver inflammation ( J:178653 )

• 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

increased liver cholesterol level ( J:178653 )

• 3 month old mutants fed a high-fat diet have 41% more hepatic cholesterol esters

increased liver triglyceride level ( J:178653 )

• 3 month old mutants fed a high-fat diet have 38% more hepatic trigylcerides than wild-type mice

liver inflammation ( J:178653 )

• aged mutants fed a high-fat diet exhibit more lobular lymphoplasmacytic inflammation, and more hepatocyte ballooning degeneration compared to wild-type mice

macrovesicular hepatic steatosis ( J:178653 )

• 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

liver fibrosis ( J:178653 )

• aged mutants fed a high-fat diet exhibit more hepatic fibrosis compared to wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:178653