The observed effect of MOR N40D in human iN cells is consistent with a number of genome wide association studies (GWAS) in humans linking OPRM1 A118G with increased alcohol response, etc. However, in the humanized mouse model, a morphine mediated decrease in mIPSC frequency in OPRM118AA mice but not in 118GG mice was observed 50. These results are likely mediated by species-specific differences in receptor expression levels or signaling mechanisms, making the elucidation of human-specific phenotypes key to understanding the role of MOR N40D in reward and addiction pathogenesis.
