Substitution at codon 269 (glutamine --> proline) of the leptin receptor (OB-R) cDNA is the only mutation found in the Zucker fatty (fa/fa) rat

Biochem Biophys Res Commun. 1996 Jul 16;224(2):597-604. doi: 10.1006/bbrc.1996.1070.

Abstract

We recently cloned one of spliced variant forms of rat leptin receptor (OB-R), which contains a short intracellular domain, and found obese-phenotype-linked nucleotide alteration in the extracellular domain of the cDNA from the Zucker (fa/fa) rat, which results in a glutamine269 to proline269 amino acid substitution. Reported herein are the cloning and sequencing of another spliced variant forms of rat OB-R cDNA with a long intracellular domain. Both forms of OB-R cDNA share the same extracellular domain. In the Zucker (fa/fa) rat, no changes in either the gene structure nor in the nucleotide sequence of the long intracellular domain were observed. However, the expression level of OB-R mRNA in the brain of Zucker (fa/fa) rat was higher than for lean littermates. These facts suggest that the substitution at codon 269 of the OB-R cDNA represents the crucial mutation which results in the obese phenotype of Zucker (fa/fa) rat.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • Codon
  • DNA Primers
  • DNA, Complementary
  • Genetic Variation
  • Glutamine*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Obesity / genetics*
  • Organ Specificity
  • Point Mutation*
  • Polymerase Chain Reaction
  • Proline*
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Rats, Zucker / genetics*
  • Receptors, Cell Surface*
  • Receptors, Leptin
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Codon
  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Leptin
  • Recombinant Proteins
  • leptin receptor, human
  • leptin receptor, mouse
  • Glutamine
  • Proline

Associated data

  • GENBANK/D84550
  • GENBANK/D84551