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

• Published in: Biochemical and biophysical research communications 1996-07, Vol.224 (2), p.597-604
• Main Authors: Iida, Mitsuru, Murakami, Takashi, Ishida, Kaori, Mizuno, Akira, Kuwajima, Masamichi, Shima, Kenji
• Format: Article
• Language: English
• Subjects: 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; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rats, Zucker - genetics; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; RNA, Messenger - biosynthesis; Sequence Homology, Amino Acid; Transcription, Genetic
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.1070

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 glutamine269to proline269amino 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.