Analysis Tools|
Allele Symbol Allele Name Allele ID |
Mc4rtm1Lowl targeted mutation 1, Bradford B Lowell MGI:3512050 |
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| Summary |
18 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• male and female homozygotes display severe early-onset obesity
(J:115192)
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• at 12 weeks, homozygotes show increased snout-anus length
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• mutants exhibit increased weight gain compared to wild-type mice when fed either the standard diet or a high-fat diet
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• mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet
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• mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet
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• mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet
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• hyperinsulinemia is displayed by homozygotes
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• mutants fed the high-fat diet exhibit increased serum leptin levels compared to wild-type mice on the same diet
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• mutants fed the high-fat diet show an increase in serum free fatty acid concentrations relative to wild-type mice
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• mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet
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• mutants fed the high-fat diet show increased serum alanine aminotransferase concentrations compared to wild-type mice
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• mice do not show an increase in oxygen consumption from stimulation by MTII as wild-type mice do
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• 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
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• mutants fed the high-fat diet exhibit decreased serum adiponectin levels compared to wild-type mice on the same diet
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• 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
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• unlike wild-type mice, mutants do not exhibit a reduction in food intake after treatment with the Mc4r inhibitor, MTII
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• obesity is accompanied by polyphagia
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• 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
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• 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
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• 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
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• mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet
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• 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
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• mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet
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• 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
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• 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
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• 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)
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• mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors
• tumors resemble hepatocellular carcinoma
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• 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
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• mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors
• tumors resemble hepatocellular carcinoma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| steatotic liver disease | DOID:9452 |
OMIM:228100 |
J:177386 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• develop obesity induced hypertension but only during active period
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• higher plasma insulin levels
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at 12 weeks, transgenic mice and wild-type littermates have the same snout-anus length, compared to increased length observed in nontransgenic Mc4rtm1Lowl mice
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• transgenic mice have increased lean mass compared with wild-type littermates, but significantly decreased lean mass compared to Mc4rtm1Lowl littermates
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• transgenic mice have increased fat mass compared with wild-type littermates, but significantly decreased fat mass compared to Mc4rtm1Lowl littermates
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• at 12 weeks of age, male and female mutants have only 37% and 46% respectively, of the obesity observed in mice homozygous for Mc4r disruption
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• mice do not show an increase in oxygen consumption from stimulation by MTII as wild-type mice do
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• oxygen consumption is reduced in the dark and light cycles compared to wild-type and is similar to Mc4rtm1Lowl homozygotes
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| N |
• transgenic mice are obese, yet show food intake comparable to wild-type mice at 11 weeks of age
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• when treated with MTII an Mc4r inhibitor, wild-type mice show a 50% reduction in food intake, while transgenic mice display no effect on intake
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice homozygous for reactivated Mc4r in the germline show normal body weights and rescue of the increased snout-anus length observed in Mc4rtm1Lowl homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice homozygous for reactivated Mc4r in neurons show normal body weights and rescue of the increased snout-anus length observed in Mc4rtm1Lowl homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• do not develop obesity induced hypertension
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• rescue of the increased weight gain, of the fat stores, of hyperphagia and of the increased linear length seen in single Mc4r homozygotes
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| N |
• mice show normalization of the hyperglycemia and hyperinsulinemia that is seen in single Mc4r homozygotes
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| N |
• rescue of the depressed respiratory exchange ratio seen in single Mc4r homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit hyperphagia
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N |
• unlike when either gene is knocked-out, mice exhibit normal growth rates
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• at 6 weeks but not 16 weeks
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 12/10/2024 MGI 6.24 |
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