protein sequence. In contrast, we generated mice expressing humanized receptors throughout this region by replacing all of exon 1, the main region of divergence between the two species (Figure 2A). Using this model, our present findings show that a key functional phenotype associated with the 118G variant, alcohol-induced striatal DA-release, is replicated across species in the absence of effects on receptor affinity, binding density, or signaling. A remaining possibility is altered oligomerization, a mechanism that is critical for opioid receptor desensitization, endocytosis, and re-insertion 57. OPRM1 A118G modifies a glycosylation site in the N-terminal extracellular loop of the receptor, and could thereby influence receptor dimerization and trafficking.
