Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice

Julie A. Brown, Streamson C. Chua, Shun Mei Liu, Matthew T. Andrews, John G. Vandenbergh

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Five allelic mutants of the diabetes (db) gene have been previously described in mice and rats causing obesity, infertility, and varying degrees of diabetes. We have identified a new, spontaneous mutation resulting in obesity and diabetes in a colony of CD-1 outbred mice, Mus musculus domesticus. Genetic complementation studies indicated that the new mutation was an allele of the diabetes locus. Sequence analysis of cDNA fragments showed a deletion of one G residue located in exon 12 of the leptin receptor gene. The mutation, Lepr(db-NCSU), results in a frameshift and reduces Lepr transcript levels 10-fold. Mutant mice drank up to four times more water and were up to two times heavier than wild-type mice. Blood glucose and plasma insulin and leptin concentrations were sexually dimorphic among affected mice, suggesting an effect of sex steroids. Mortality of affected males was 100% by 5 mo, whereas affected females survived up to 10 mo of age.

Original languageEnglish (US)
Pages (from-to)R320-R330
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume278
Issue number2 47-2
DOIs
StatePublished - Feb 2000
Externally publishedYes

Keywords

  • Insulin
  • Leptin
  • Mouse
  • Phenotype

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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