Leptin receptor mutations in 129 db super(3J)/db super(3J) mice and NIH fa super(cp)/fa super(cp) rats

• Published in: Mammalian genome 1997-06, Vol.8 (6), p.445-447
• Main Authors: Lee, G-H, Li, C, Montez, J, Halaas, J, Darvishzadeh, J, Friedman, J M
• Format: Article
• Language: English
• ISSN: 0938-8990

The cloning of leptin and its receptor have led to the identification of a novel signal transduction pathway important in body weight regulation. Previous data have indicated that the db gene encodes several alternatively spliced forms of the receptor for the ob gene product, leptin. Of these splice forms, only one, Ob-Rb, contains a long cytoplasmic domain, which includes motifs implicated in signal transduction. Ob-Rb is highly expressed in the hypothalamus and is abnormally spliced in C57BL/Ks db/db mice. This mutation results in the truncation of the Ob-Rb splice form and loss of its signal transducing capability. Recently a missense mutation in Lepr was identified in the fatty (fa/fa) Zucker rat. This mutation presumably alters the binding of leptin at the cell surface. Mutations in the mouse db locus and its rat homolog, fatty, have independently arisen many times. The molecular basis of the mutations in these other mutant strains could provide information on the structure-function relationship of leptin and Lepr. Here we report the molecular basis of the mutations in the coding regions of Lepr from mutant 129 db super(3J)/db super(3J) rats and NIH fa super(cp) /fa super(cp) rats.