About   Help   FAQ
Phenotypes Associated with This Genotype
Genotype
MGI:3692534
Allelic
Composition
Mc4rtm1Lowl/Mc4rtm1Lowl
Genetic
Background
involves: 129S4/SvJae * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mc4rtm1Lowl mutation (2 available); any Mc4r mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• male and female homozygotes display severe early-onset obesity (J:115192)
• at 12 weeks, homozygotes show increased snout-anus length
• mutants exhibit increased weight gain compared to wild-type mice when fed either the standard diet or a high-fat diet
• mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet
• mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet

homeostasis/metabolism
• mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet
• hyperinsulinemia is displayed by homozygotes
• mutants fed the high-fat diet exhibit increased serum leptin levels compared to wild-type mice on the same diet
• mutants fed the high-fat diet show an increase in serum free fatty acid concentrations relative to wild-type mice
• mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet
• mutants fed the high-fat diet show increased serum alanine aminotransferase concentrations compared to wild-type mice
• mice do not show an increase in oxygen consumption from stimulation by MTII as wild-type mice do
• 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
• mutants fed the high-fat diet exhibit decreased serum adiponectin levels compared to wild-type mice on the same diet
• 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
• unlike wild-type mice, mutants do not exhibit a reduction in food intake after treatment with the Mc4r inhibitor, MTII
• obesity is accompanied by polyphagia

adipose tissue
• 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 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 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
• mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet
• 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
• mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet
• 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
• 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
• 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)
• 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
• mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors
• tumors resemble hepatocellular carcinoma

neoplasm
• 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)
fatty liver disease DOID:9452 OMIM:228100
J:177386


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
Citing These Resources
Funding Information
Warranty Disclaimer & Copyright Notice
Send questions and comments to User Support.
last database update
01/18/2022
MGI 6.17
The Jackson Laboratory