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恒河猴中μ-阿片受体的人类表达变异情况与之相似。

Human expression variation in the mu-opioid receptor is paralleled in rhesus macaque.

作者信息

Vallender Eric J, Priddy Cassandra M, Chen Guo-Lin, Miller Gregory M

机构信息

Division of Neurochemistry, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.

出版信息

Behav Genet. 2008 Jul;38(4):390-5. doi: 10.1007/s10519-008-9207-2. Epub 2008 Apr 1.

Abstract

The mu-opioid receptor is a key component in many neurobiological systems including those affecting perceptions of pain and pleasure. In humans and non-human primate model systems, genetic variation in the receptor has been associated with numerous behavioral and physiological traits. In humans, polymorphisms have been identified which affect not only the biochemical function of the receptor, but also expression level. Existing rhesus macaque variation parallels the functional protein changes seen in human, but it remains unknown if expression level differences or concomitant protein changes may also exist. Here we perform a comprehensive survey of naturally occurring polymorphisms in Indian-origin rhesus macaques and identify three 5' UTR haplotypes with effects on expression level. These expression level effects are in linkage disequilibrium with the previously identified rhesus coding polymorphism C77G. The C77G polymorphism in rhesus parallels the functional effects of the A118G polymorphism in humans and expression level differences occur within both species. Together, the functional variations reported here have implications for future studies seeking to model the opioid system and its associated phenotypes in rhesus macaques.

摘要

μ-阿片受体是许多神经生物学系统的关键组成部分,包括那些影响疼痛和愉悦感知的系统。在人类和非人类灵长类动物模型系统中,该受体的基因变异与众多行为和生理特征相关。在人类中,已鉴定出多态性,其不仅影响受体的生化功能,还影响表达水平。现有的恒河猴变异与人类中观察到的功能性蛋白质变化相似,但尚不清楚是否也存在表达水平差异或伴随的蛋白质变化。在此,我们对印度恒河猴中自然发生的多态性进行了全面调查,并鉴定出三种对表达水平有影响的5' UTR单倍型。这些表达水平效应与先前鉴定的恒河猴编码多态性C77G处于连锁不平衡状态。恒河猴中的C77G多态性与人类中的A118G多态性的功能效应相似,且两个物种中均存在表达水平差异。总之,本文报道的功能变异对未来旨在在恒河猴中模拟阿片系统及其相关表型的研究具有启示意义。

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