Abnormal splicing of the leptin receptor in diabetic mice

GH Lee, R Proenca, JM Montez, KM Carroll… - Nature, 1996 - nature.com
GH Lee, R Proenca, JM Montez, KM Carroll, JG Darvishzadeh, JI Lee, JM Friedman
Nature, 1996nature.com
MUTATIONS in the mouse diabetes (db) gene result in obesity and diabetes in a syndrome
resembling morbid human obesity1. Previous data suggest that the db gene encodes the
receptor for the obese (ob) gene product, leptin2–7. 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 8. 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 …
Abstract
MUTATIONS in the mouse diabetes(db) gene result in obesity and diabetes in a syndrome resembling morbid human obesity1. Previous data suggest that the db gene encodes the receptor for the obese(ob) gene product, leptin2–7. A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6-cM interval on mouse chromosome 4 as db8. 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.
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