ANATOMIC LOCALIZATION OF ALTERNATIVELY SPLICED LEPTIN RECEPTORS (OB-R) IN MOUSE-BRAIN AND OTHER TISSUES

Leptin's effects are mediated by interactions with a receptor that is alternatively spliced, resulting in at least five different murine for ms: Ob-Ra, Ob-Rb, Ob-Rc, Ob-Rd, and Ob-Re, A mutation in one splice fo rm, Ob-Rb, results in obesity in mice, Northern blots, RNase protectio n assays, and PCR indicate that Ob-Rb is expressed at a relatively hig h level in hypothalamus and low level in several other tissues, Ob-Ra is expressed ubiquitously, whereas Ob-Rc, -Rd, and -Re RNAs are only d etectable using PCR, In hypothalamus, Ob-Rb is present in the arcuate, ventromedial, dorsomedial, and lateral hypothalamic nuclei but is not detectable in other brain regions, These nuclei are known to regulate food intake and body weight. The level of Ob-Rb in hypothalamus is re duced in mice rendered obese by gold thioglucose (GTG), which causes h ypothalamic lesions, The obesity in GTG treated mice is likely to be c aused by ablation of Ob-Rb-expressing neurons, which results in leptin resistance.