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 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.
Takaya
K
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Ogawa
Y
Y
Isse
N
N
Okazaki
T
T
Satoh
N
N
Masuzaki
H
H
Mori
K
K
Tamura
N
N
Hosoda
K
K
Nakao
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics*; D009928:Organ Specificity; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker / Q000235:genetics*; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D054411:Receptors, Leptin; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C515448:LEPR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; C515447:leptin receptor, mouse