MOLECULAR-CLONING OF RAT LEPTIN RECEPTOR ISOFORM COMPLEMENTARY DNAS -IDENTIFICATION OF A MISSENSE MUTATION IN ZUCKER FATTY (FA FA) RATS/

We cloned the full-length rat leptin receptor (Ob-R) isoform complemen tary DNAs (cDNAs) and examined the gene expression in rats. We also id entified a mutation in Ob-R in Zucker fatty (fa/fa) rats. Three altern atively spliced isoforms (Ob-Ra, Ob-Rb, and Ob-Re) have been identifie d, which are closely related to the gp130 signal-transduction componen t of class I cytokine receptors. Rat Ob-Ra and Ob-Rb were single trans membrane proteins, which differ in the C-terminal amino acid sequences . On the other hand, Ob-Re had no transmembrane domain and was a solub le form of the receptor. Reverse transcription-polymerase chain reacti on analysis revealed that Ob-R isoform messenger RNAs (mRNAs) are expr essed in a wide variety of rat tissues in tissue-specific manners. A m issense 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 prese nt in the brain from Zucker fatty (fa/fa) rats at comparable amounts t o those in their lean littermates. The present study provides new insi ght into the molecular mechanisms for Ob-R. (C) 1996 Academic Press, I nc.