STRUCTURE, TISSUE DISTRIBUTION, AND CHROMOSOMAL LOCALIZATION OF THE PREPRONOCICEPTIN GENE

Nociceptin (orphanin FQ), the newly discovered natural agonist: of opi oid receptor-like (ORL(r)) receptor, is a neuropeptide that is endowed with pronociceptive activity in vivo. Nociceptin is derived from a la rger precursor, prepronociceptin (PPNOC), whose human, mouse, and rat genes we have now isolated. The PPNOC gene is highly conserved in the three species and displays organizational features that are strikingly similar to those of the genes of preproenkephalin, preprodynorphin, a nd preproopiomelanocortin, the precursors to endogenous opioid peptide s, suggesting the four genes belong to the same family-i.e., have a co mmon evolutionary origin. The PPNOC gene encodes a single copy of noci ceptin as well as of other peptides whose sequence is strictly conserv ed across murine and human species; hence it is likely to neurophysiol ogically significant. Northern blot analysis shows that the PPNOC gene is predominantly transcribed in the central nervous system (brain and spinal cord) and, albeit weakly, in the ovary, the sole peripheral or gan expressing the gene. By using a radiation hybrid cell line panel, the PPNOC gene was mapped to the short arm of human chromosome 8 (8p21 ), between sequence-tagged site markers WI-5833 and WI-1172, in close proximity of the locus encoding the neurofilament light chain NEFL. An alysis of yeast artificial chromosome clones belonging to tile WC8,4 c ontig covering the 8p21 region did not allow to detect the presence of the gene on these feast artificial chromosomes, suggesting a gap in t he coverage within this contig.