Abstract
Full‐length 7‐transmembrane (TM) variants of mu opioid receptor (MOR) share similar amino acid sequences of TM domains in rodents and humans; however, interspecies differences in N‐ and C‐terminal amino acid sequences of MOR splice variants dramatically affect the downstream signaling. Thus, it is essential to develop a mouse model that expresses human MOR for opioid pharmacological studies. We generated two lines of fully humanized MOR mice, line #1 and #2. The novel murine model having human OPRM1 genes and human‐specific variants was examined by RT‐PCR. Humanized MOR mice were characterized in vivo using a tail‐flick, charcoal meal, open field, tail suspension, naloxone precipitation tests, and rectal temperature measurement. The data indicated that wild‐type (WT) and humanized MOR mice exhibited different pharmacology of morphine, including antinociception, tolerance, sedation, and withdrawal syndromes, suggesting the presence of species difference between mouse and human MORs. Therefore, humanized MOR mice could serve as a novel mouse model for pharmacogenetic studies of opioids.
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