First Author | Brown JA | Year | 2000 |
Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 278 |
Issue | 2 | Pages | R320-30 |
PubMed ID | 10666131 | Mgi Jnum | J:60363 |
Mgi Id | MGI:1353209 | Doi | 10.1152/ajpregu.2000.278.2.R320 |
Citation | Brown JA, et al. (2000) Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice. Am J Physiol Regul Integr Comp Physiol 278(2):R320-30 |
abstractText | 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. |