Isolation and structural and genetic analysis of the mouse enkephalin geneand its d(AC/TG)(n) repeats

Enkephalins, the endogenous opioids, mediate a wide variety of intercellula r communications through ontogeny and their involvement has been suggested in drug addiction and alcohol abuse as well as in various neuropsychiatric disorders. In order to generate a genetic model, we have isolated the mouse enkephalin (mENK) gene, analyzed its regulatory region and compared its st ructure to the well characterized rat ENK (rENK) gene. We analyzed 2600 bp and found 3 highly homologous regions: The highest level (98%) of positiona l and sequence homology between mice and rats was in the TATA/proximal regu latory region. This region contains all the inducible regulatory elements ( enkCRE1, NF1, AP-2, NFkB, etc.) and also an octamer-like element at -543 bp . This high homology is interrupted in both mice and rats by the typically polymorphic d(AC/TG)(n) and d(TC/GA)(n) dinucleotide repeats positioned bet ween nucleotides -670 and -950. The position and orientation of these repet itive elements differ substantially in the two species. Genomic PCR analysi s of the d(AC/TG)(n) repeat in various mouse strains, including aberrant be havioral or neurological phenotypes, showed lack of polymorphism at this re peat. The positional and sequence homologies between the rat and the mouse ENK genes decrease in more upstream regions due to the presence of nonhomol ogues repetitive DNA sequences.