Our humanized mouse line model differs from that of Blendy and colleagues who first reported a murine model of the A118G polymorphism34. In that model, the equivalent nucleotide substitution was performed at position 112 (A112G) of the MOR gene. The result was a similar amino acid substitution (N38D) at the N-terminus and the loss of the putative glycosylation site. However, whereas the receptor polymorphism in humans results in the loss of 1 of 5 putative glycosylation sites (our mouse model), the polymorphism in Blendy’s model removes 1 of 4 glycosylation sites. Nevertheless, our electrophysiological and behavioral studies with morphine are in agreement with their observations of the morphine-mediated anti-nociception with the hot-plate assay. In a cumulative dosing paradigm, they found that 112GG carriers exhibited a significantly lower maximal possible effect of morphine34. These results suggest that morphine’s effects in mutant receptor carriers will be manifested with either three or four glycosylation sites. The loss of the glycosylation site may be significant in decreasing the opioid receptor’s ability to dimerize with other opioid receptors35. For example, the loss of the glycosylation
