Leptin exerts its metabolic effects by binding to the leptin receptor (Ob-R). In humans the promoter of, the Ob-R gene-related protein (Ob-RGRP) gene and the B219/Ob-R promoter have been speculated to spatially and temporarily regulate Ob-R gene transcription; however, the promoter function of the Ob-R gene has not been directly analyzed. Using 5' rapid amplification of the cDNA end we isolated novel ob-r tran, scripts starting from the 3' portions of the B219/ob-r 5'-untranslated region in the adult mouse brain. The proximal promoter containing these start sites showed robust activity in neuron-derived, but not non-neuronal cell lines. The promoter activity was comparable with that of the ob-rgrp promoter in a neuronal cell. but significantly weaker in non-neuronal cells. Deletion analyses identifying two enhancer elements were located in this promoter. The identification of a novel ob-r gene promoter might provide a useful tool to study neuron specific expression and hormonal regulation of the ob-r gene. (C) 2009 Elsevier Inc. All rights reserved.