Despite information gained from human post mortem tissues, a full understanding of the OPRM1 A118G polymorphism requires extensive biochemical characterization aligned with behavioral analysis, which is not feasible in human subjects. The mouse is a tractable model system to study behavioral effects of this SNP while at the same time allowing for detailed molecular and biochemical analysis in vivo. Homologous recombination technology can now be used to generate point mutations in mice for those genes in which human SNPs have been identified. This approach, however, has not been fully utilized due in part to the labor-intensive procedures involved in building the complex targeting vectors required. Recent advances and the availability of bacterial artificial chromosome (BAC) vectors have streamlined this process, making the use of knock-in mice a natural progression to investigate human disease. To gain insight into the role of the A118G variant in humans, we have generated the equivalent point mutation in mice, A112G, which alters the same amino acid coding from an asparagine to aspartic acid at position 38 (Asn38Asp; N38D), eliminating an N-linked glycosylation site.
