Abnormal Splicing of the Leptin Receptor in Diabetic Mice

Nature. 1996 Feb 15;379(6566):632-5. doi: 10.1038/379632a0.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Chromosome Mapping
  • DNA Primers
  • Diabetes Mellitus, Experimental / genetics*
  • Leptin
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Proteins*
  • Receptors, Cell Surface*
  • Receptors, Leptin
  • Tissue Distribution

Substances

  • Carrier Proteins
  • DNA Primers
  • Leptin
  • Proteins
  • Receptors, Cell Surface
  • Receptors, Leptin
  • leptin receptor, human
  • leptin receptor, mouse

Associated data

  • GENBANK/U49106
  • GENBANK/U49107
  • GENBANK/U49108
  • GENBANK/U49109
  • GENBANK/U49110