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

Kazuhiko Takaya, Yoshihiro Ogawa, Naohi Isse, Taku Okazaki, Noriko Satoh, Hiroaki Masuzaki, Kiyoshi Mori, Naohisa Tamura, Kiminori Hosoda, Kazuwa Nakao

Research output: Contribution to journalArticlepeer-review

226 Citations (Scopus)

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 Gin 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.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume225
Issue number1
DOIs
Publication statusPublished - Aug 5 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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