Phenotypes Associated with This Genotype

Genotype
MGI:6405042

• Allelic Composition: Mc4r^tm1Matsu/Mc4r^tm1Matsu
• Genetic Background: C57BL/6J-Mc4r^tm1Matsu

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

growth/size/body

increased susceptibility to diet-induced obesity ( J:285412 )

♂ • body weight of mice fed a Western diet is 1.8x greater than that of lean control mice

♂ • mutant mice fed a Western diet treated with GS-0976, a liver-targeted inhibitor of ACC1/2, show suppressed weight gain, without affecting food intake

increased liver weight ( J:285412 )

♂ • liver weights are 4.3-fold higher than in lean control mice on a Western diet

behavior/neurological

increased food intake ( J:285412 )

♂ • cumulative caloric intake of mutant mice is 1.5 times higher compared to control mice on a Western diet

liver/biliary system

increased liver weight ( J:285412 )

♂ • liver weights are 4.3-fold higher than in lean control mice on a Western diet

increased liver triglyceride level ( J:285412 )

♂ • hepatic triglyceride content is 12-fold higher than in lean control mice on a Western diet

♂ • however, plasma triglyceride concentrations in Western diet-fed mice are similar to lean controls

liver inflammation ( J:285412 )

♂ • weak lobular inflammation is seen in Western diet-fed mice

♂ • mice show increased hepatic gene expression related to inflammation

hepatic steatosis ( J:285412 )

♂ • Western diet-fed mice show increased hepatic steatosis

♂ • GS-0976 treatment lowers steatosis

liver fibrosis ( J:285412 )

♂ • hepatic fibrosis is exacerbated during 9 weeks of Western diet feeding

♂ • mice show increased hepatic gene expression related to fibrosis

♂ • GS-0976 treatment suppresses the progression of fibrosis

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:285412 )

♂ • body weight of mice fed a Western diet is 1.8x greater than that of lean control mice

♂ • mutant mice fed a Western diet treated with GS-0976, a liver-targeted inhibitor of ACC1/2, show suppressed weight gain, without affecting food intake

increased hydroxyproline level ( J:285412 )

♂ • hepatic hydroxyproline content is 1.9-fold increased after 9 weeks of Western diet feeding

♂ • GS-0976 treatment lowers hydroxyproline content

increased circulating insulin level ( J:285412 )

♂ • mice fed a Western diet develop hyperinsulinemia, although they maintain normoglycemia

♂ • treatment with GS-0976 increases plasma insulin concentrations

increased circulating cholesterol level ( J:285412 )

♂ • total cholesterol concentrations are 4x higher than in controls when fed a Western diet

♂ • treatment with GS-0976 lowers plasma total cholesterol levels

increased circulating alanine transaminase level ( J:285412 )

♂ • mice fed a Western diet show higher plasma ALT levels

♂ • treatment with GS-0976 lowers plasma ALT levels

increased circulating aspartate transaminase level ( J:285412 )

♂ • mice fed a Western diet show higher AST levels

♂ • treatment with GS-0976 lowers plasma AST levels

increased liver triglyceride level ( J:285412 )

♂ • hepatic triglyceride content is 12-fold higher than in lean control mice on a Western diet

♂ • however, plasma triglyceride concentrations in Western diet-fed mice are similar to lean controls

immune system

liver inflammation ( J:285412 )

♂ • weak lobular inflammation is seen in Western diet-fed mice

♂ • mice show increased hepatic gene expression related to inflammation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
metabolic dysfunction-associated steatohepatitis		DOID:0080547		J:285412