C. Mollereau et al., STRUCTURE, TISSUE DISTRIBUTION, AND CHROMOSOMAL LOCALIZATION OF THE PREPRONOCICEPTIN GENE, Proceedings of the National Academy of Sciences of the United Statesof America, 93(16), 1996, pp. 8666-8670
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.