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Abnormal splicing of the leptin receptor in diabetic mice

Nature volume 379, pages 632–635 (1996)Cite this article

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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Authors and Affiliations

  1. Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

    Gwo-Hwa Lee, R. Proenca, J. I. Lee & J. M. Friedman

  2. Department of Molecular Genetics, The Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

    Gwo-Hwa Lee, R. Proenca, J. M. Montez, K. M. Carroll, J. G. Darvishzadeh & J. M. Friedman

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  1. Gwo-Hwa Lee
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Lee, GH., Proenca, R., Montez, J. et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635 (1996). https://doi.org/10.1038/379632a0

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