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Am J Physiol Regul Integr Comp Physiol 278: R320-R330, 2000;
0363-6119/00 $5.00
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Vol. 278, Issue 2, R320-R330, February 2000

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

Julie A. Brown1, Streamson C. Chua Jr.2, Shun Mei Liu2, Matthew T. Andrews3, and John G. Vandenbergh1

1 Department of Zoology, North Carolina State University, Raleigh 27695-7617; 3 Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695-7614; and 2 Columbia University, R. Berrie Pavilion, New York, New York 10032

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, Leprdb-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.

leptin; phenotype; mouse; insulin


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