Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice.
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.
Brown
J A
JA
Department of Zoology, North Carolina State University, Raleigh 27695-7617, North Carolina, USA.
Chua
S C
SC
Liu
S M
SM
Andrews
M T
MT
Vandenbergh
J G
JG
D000483:Alleles; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology; D004326:Drinking; D004435:Eating; D005740:Gases / Q000097:blood; D015870:Gene Expression / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000502:physiology; D020738:Leptin / Q000097:blood; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D002352:Carrier Proteins; D005740:Gases; D007328:Insulin; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin