Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice

Cell. 1996 Feb 9;84(3):491-5. doi: 10.1016/s0092-8674(00)81294-5.

Abstract

OB-R is a high affinity receptor for leptin, an important circulating signal for the regulation of body weight. We identified an alternatively spliced transcript that encodes a form of mouse OB-R with a long intracellular domain. db/db mice also produce this alternatively spliced transcript, but with a 106 nt insertion that prematurely terminates the intracellular domain. We further identified G --> T point mutation in the genomic OB-R sequence in db/db mice. This mutation generates a donor splice site that converts the 106 nt region to a novel exon retained in the OB-R transcript. We predict that the long intracellular domain form of OB-R is crucial for initiating intracellular signal transduction, and as a corollary, the inability to produce this form of OB-R leads to the severe obese phenotype found in db/db mice.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Humans
  • Leptin
  • Mice
  • Mice, Inbred Strains
  • Mice, Obese
  • Molecular Sequence Data
  • Obesity / genetics
  • Obesity / metabolism
  • Phenotype
  • Point Mutation*
  • Polymerase Chain Reaction
  • Proteins / metabolism*
  • Receptors, Cell Surface*
  • Receptors, Cytokine / genetics*
  • Receptors, Leptin
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

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

Associated data

  • GENBANK/U46135