Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats

Biochem Biophys Res Commun. 1996 Aug 5;225(1):75-83. doi: 10.1006/bbrc.1996.1133.

Abstract

We cloned the full-length rat leptin receptor (Ob-R) isoform complementary DNAs (cDNAs) and examined the gene expression in rats. We also identified a mutation in Ob-R in Zucker fatty (fa/fa) rats. Three alternatively spliced isoforms (Ob-Ra, Ob-Rb, and Ob-Re) have been identified, which are closely related to the gp130 signal-transduction component of class I cytokine receptors. Rat Ob-Ra and Ob-Rb were single transmembrane proteins, which differ in the C-terminal amino acid sequences. On the other hand, Ob-Re had no transmembrane domain and was a soluble form of the receptor. Reverse transcription-polymerase chain reaction analysis revealed that Ob-R isoform messenger RNAs (mRNAs) are expressed in a wide variety of rat tissues in tissue-specific manners. A missense mutation (an A to C conversion at nucleotide position 806) was found in the extracellular domain of all the isoforms in Zucker fatty (fa/fa) rats, which resulted in an amino acid change from Gln to Pro at + 269 (the Gln269Pro mutation). These Ob-R isoform mRNAs were present in the brain from Zucker fatty (fa/fa) rats at comparable amounts to those in their lean littermates. The present study provides new insight into the molecular mechanisms for Ob-R.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • Gene Expression
  • Humans
  • Male
  • Mice
  • Mice, Obese
  • Molecular Sequence Data
  • Obesity / genetics*
  • Organ Specificity
  • Point Mutation*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Zucker / genetics*
  • Receptors, Cell Surface*
  • Receptors, Cytokine / biosynthesis
  • Receptors, Cytokine / genetics
  • Receptors, Leptin
  • Sequence Homology, Amino Acid

Substances

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

Associated data

  • GENBANK/D85557
  • GENBANK/D85558
  • GENBANK/D85559