Mice homozygous for this mutation exhibit moderate obesity and extreme diabetes. The primary investigator reports blood glucose levels reaching 600-850 mg/ml and low plasma insulin levels (1-4 ng/ml). Pancreatic beta cells are small, degranulated and atrophic. The liver is steatotic and strongly PAS-positive for glycogen. Adrenal glands are large with a hyperplastic zona reticularis and appear to be missing the medulla.
Homozygous females have fewer primary oocytes and follicles, as well as a decreased amount of developing and ovulated follicles. Fecundity is decreased resulting in smaller litter sizes and fewer litters.
This spontaneous mutation arose at The Jackson Laboratory on a mixed C57BL/6J, SWR/J and CBA background. The mutation was mapped to Chromosome 4 and complementation testing in the laboratory of Dr. Jurgen Naggert demonstrated that it was a remutation at Leprdb. The strain was cryopreserved in 2007.
|Allele Name||diabetes 9 Jackson|
|Gene Symbol and Name||Lepr, leptin receptor|
|Strain of Origin||mixed|
|General Note||This mutation arose spontaneously in mice of a mixed genetic background (~46% C57BL/6, ~50% SWR, and ~3% CBA estimated from the breeding records).|
|Molecular Note||This mutation was shown to be an allele of the leptin receptor gene by its failure to complement the original diabetes mutation, Leprdb.|