國家衛生研究院 NHRI:Item 3990099045/12508
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    题名: Morphine produces potent antinociception, sedation, and hypothermia in humanized mice expressing human mu opioid receptor splice variants
    作者: Huang, YH;Wu, YW;Chuang, JY;Chang, YC;Chang, HF;Tao, PL;Loh, HH;Yeh, SH
    贡献者: Institute of Biotechnology and Pharmaceutical Research;NHRI Graduate Student Program;Center for Neuropsychiatric Research
    摘要: Morphine is a strong painkiller acting through mu opioid receptor (MOR). Full-length 7-transmembrane (TM) variants of 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 splice variants for opioid pharmacological studies. We generated two lines of fully humanized MOR mice (hMOR; mMOR mice), line #1 and #2. The novel murine model having human OPRM1 genes and human-specific variants was examined by reverse transcription polymerase chain reaction (RT-PCR) and the MinION nanopore sequencing. The differences in the regional distribution of MOR between wild-type (WT) and humanized MOR mice brains were detected by RNAscope and radioligand binding assay. hMOR; mMOR 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 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, hMOR; mMOR mice could serve as a novel mouse model for pharmacogenetic studies of opioids.
    日期: 2020-06
    關聯: Pain. 2020 Jun;161(6):1177-1190.
    Link to: http://dx.doi.org/10.1097/j.pain.0000000000001823
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0304-3959&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000539257100007
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85084921513
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