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 language | English (US) |
---|---|
Pages (from-to) | R320-R330 |
Journal | American Journal of Physiology - Regulatory Integrative and Comparative Physiology |
Volume | 278 |
Issue number | 2 47-2 |
DOIs | |
State | Published - Feb 2000 |
Externally published | Yes |
Keywords
- Insulin
- Leptin
- Mouse
- Phenotype
ASJC Scopus subject areas
- Physiology
- Physiology (medical)