Laboratory of Molecular Genetics
Abnormal splicing of the leptin receptor in diabetic mice.
Lee GH. Proenca R. Montez JM. Carroll KM. Darvishzadeh JG. Lee JI. Friedman JM.
Abstract
Mutations in the mouse diabetes (db) gene result in obesity and
diabetes in a syndrome resembling morbid human obesity. Previous
data suggest that the db gene encodes the receptor for the obese
(ob) gene product, leptin. A leptin receptor was recently cloned
from choroid plexus and shown to map to the same 6-cM interval
on mouse chromosome 4 as db. This receptor maps to the same 300-kilobase
interval as db, and has at least six alternatively spliced forms.
One of these splice variants is expressed at a high level in the
hypothalamus, and is abnormally spliced in C57BL/Ks db/db mice.
The mutant protein is missing the cytoplasmic region, and is likely
to be defective in signal transduction. This suggests that the
weight-reducing effects of leptin may be mediated by signal transduction
through a leptin receptor in the hypothalamus.
