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TY - JOUR AU - Lee, Gwo-Hwa AU - Proenca, R. AU - Montez, J. M. AU - Carroll, K. M. AU - Darvishzadeh, J. G. AU - Lee, J. I. AU - Friedman, J. M. PY - 1996 DA - 1996/02/01 TI - Abnormal splicing of the leptin receptor in diabetic mice JO - Nature SP - 632 EP - 635 VL - 379 IS - 6566 AB - 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. SN - 1476-4687 UR - https://doi.org/10.1038/379632a0 DO - 10.1038/379632a0 ID - Lee1996 ER -