title: 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.
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.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, University of Tokushima, Japan. mura@clin.med.tokushima-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Iida
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Ishida
authors.forename: A
authors.initials: A
authors.lastname: Mizuno
authors.forename: M
authors.initials: M
authors.lastname: Kuwajima
authors.forename: K
authors.initials: K
authors.lastname: Shima
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; D014644:Genetic Variation; D005973:Glutamine; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics*; D009928:Organ Specificity; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011392:Proline; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011924:Rats, Zucker / Q000235:genetics*; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; C515448:LEPR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D005973:Glutamine; D011392:Proline