Phenotypes Associated with This Genotype

Genotype
MGI:3692534

• Allelic Composition: Mc4r^tm1Lowl/Mc4r^tm1Lowl
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

growth/size/body

obese ( J:115192 , J:177386 )

• male and female homozygotes display severe early-onset obesity (J:115192)

increased body length ( J:115192 )

• at 12 weeks, homozygotes show increased snout-anus length

increased susceptibility to weight gain ( J:177386 )

• mutants exhibit increased weight gain compared to wild-type mice when fed either the standard diet or a high-fat diet

increased susceptibility to diet-induced obesity ( J:177386 )

• mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet

increased liver weight ( J:177386 )

• mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:177386 )

• mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet

increased circulating insulin level ( J:115192 )

• hyperinsulinemia is displayed by homozygotes

increased circulating leptin level ( J:177386 )

• mutants fed the high-fat diet exhibit increased serum leptin levels compared to wild-type mice on the same diet

increased circulating free fatty acids level ( J:177386 )

• mutants fed the high-fat diet show an increase in serum free fatty acid concentrations relative to wild-type mice

increased circulating interleukin-6 level ( J:177386 )

• mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet

increased circulating alanine transaminase level ( J:177386 )

• mutants fed the high-fat diet show increased serum alanine aminotransferase concentrations compared to wild-type mice

abnormal oxygen consumption ( J:115192 )

• mice do not show an increase in oxygen consumption from stimulation by MTII as wild-type mice do

decreased oxygen consumption ( J:115192 )

• oxygen consumption is reduced in the dark and light cycles compared to wild-type and is similar to mutants also expressing Tg(Sim1-cre)1Lowl

decreased circulating adiponectin level ( J:177386 )

• mutants fed the high-fat diet exhibit decreased serum adiponectin levels compared to wild-type mice on the same diet

increased liver triglyceride level ( J:177386 )

• mutants exhibit increased hepatic triglyceride content compared to wild-type mice on either the standard or high-fat diet

• livers of mutants fed the high-fat diet exhibit increased triglyceride secretion compared to wild-type livers

behavior/neurological

abnormal food intake ( J:115192 )

• unlike wild-type mice, mutants do not exhibit a reduction in food intake after treatment with the Mc4r inhibitor, MTII

polyphagia ( J:115192 )

• obesity is accompanied by polyphagia

adipose tissue

increased total body fat amount ( J:177386 )

• mutants fed the standard diet exhibit increased adiposity compared to wild-type mice on the same diet

• mutants fed the high-fat diet also exhibit increased adiposity, but only up to 8 weeks of high-fat feeding with no further increase after 8 weeks

white adipose tissue inflammation ( J:177386 )

• white adipose tissue of mutants fed the high-fat diet for 8 weeks exhibits increased macrophage infiltration and pro-inflammatory cytokine expression compared to wild-type white adipose tissue

immune system

white adipose tissue inflammation ( J:177386 )

• white adipose tissue of mutants fed the high-fat diet for 8 weeks exhibits increased macrophage infiltration and pro-inflammatory cytokine expression compared to wild-type white adipose tissue

increased circulating interleukin-6 level ( J:177386 )

• mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet

liver inflammation ( J:177386 )

• livers from mutants fed the high-fat diet exhibit ballooning degeneration and massive infiltration of inflammatory cells

• livers from mutants fed the high-fat diet exhibit increased inflammatory cell infiltration compared to wild-type livers

liver/biliary system

increased liver weight ( J:177386 )

• mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet

increased liver triglyceride level ( J:177386 )

• mutants exhibit increased hepatic triglyceride content compared to wild-type mice on either the standard or high-fat diet

• livers of mutants fed the high-fat diet exhibit increased triglyceride secretion compared to wild-type livers

liver inflammation ( J:177386 )

• livers from mutants fed the high-fat diet exhibit ballooning degeneration and massive infiltration of inflammatory cells

• livers from mutants fed the high-fat diet exhibit increased inflammatory cell infiltration compared to wild-type livers

microvesicular hepatic steatosis ( J:177386 )

• mutants fed the high-fat diet for 8 weeks exhibit massive microvesicular steatosis in the centrilobular and portal areas while wild-type mice only have minimal lipid accumulation in the liver

• mutants fed the high-fat diet develop liver steatosis faster (by 8 weeks of high-fat diet) than wild-type mice (by 20 weeks of high-fat diet)

increased hepatocellular carcinoma incidence ( J:177386 )

• mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors

• tumors resemble hepatocellular carcinoma

liver fibrosis ( J:177386 )

• livers from mutants fed the high-fat diet exhibit increased pericellular fibrosis compared to wild-type mice at 8 and 20 weeks of high-fat feeding

neoplasm

increased hepatocellular carcinoma incidence ( J:177386 )

• mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors

• tumors resemble hepatocellular carcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
steatotic liver disease		DOID:9452	OMIM:228100	J:177386