Directional tag PCR substractive hybridization was used to construct a rat hypothalamic cDNA library from which cerebellar and hippocampal sequences had been depleted. Hypocretin, one of several novel hypothalamic-specific polypeptides identified, isolated and sequenced, is localized to regions of the hypothalamus involved in appetite and feeding behavior. Hypocretin polypeptides are biologically active, producing electrical changes in neurons, lowering body temperature and reducing food intake. The invention provides hypocretin polynucleotides and hypocretin polypeptides as well as antibodies, oligonucleotides, diagnostic kits and methods, and therapeutic compositions and methods.
HYPOTHALAMUS-SPECIFIC POLYPEPTIDES