IDENTIFICATION AND EXPRESSION CLONING OF A LEPTIN RECEPTOR, OB-R

The ob gene product, leptin, is an important circulating signal for th e regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusio n proteins as well as [I-125]leptin. After a binding survey of cell li nes and tissues, we identified leptin-binding sites in the mouse choro id plexus. A cDNA expression library was prepared from mouse choroid p lexus and screened with a leptin-AP fusion protein to identify a lepti n receptor (OB-R). OB-R is a single membrane-spanning receptor most re lated to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not o nly in choroid plexus, but also in several other tissues, including hy pothalamus. Genetic mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of mouse chromosome 4 that contains the db locus.