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μ阿片受体基因(OPRM1)可变剪接变体mRNA在四种近交系小鼠品系脑区中的差异表达

Differential expressions of the alternatively spliced variant mRNAs of the µ opioid receptor gene, OPRM1, in brain regions of four inbred mouse strains.

作者信息

Xu Jin, Lu Zhigang, Xu Mingming, Rossi Grace C, Kest Benjamin, Waxman Amanda R, Pasternak Gavril W, Pan Ying-Xian

机构信息

Department of Neurology and Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.

Department of Psychology, Long Island University, Post Campus, Brookville, New York, United States of America.

出版信息

PLoS One. 2014 Oct 24;9(10):e111267. doi: 10.1371/journal.pone.0111267. eCollection 2014.

Abstract

The µ opioid receptor gene, OPRM1, undergoes extensive alternative pre-mRNA splicing in rodents and humans, with dozens of alternatively spliced variants of the OPRM1 gene. The present studies establish a SYBR green quantitative PCR (qPCR) assay to more accurately quantify mouse OPRM1 splice variant mRNAs. Using these qPCR assays, we examined the expression of OPRM1 splice variant mRNAs in selected brain regions of four inbred mouse strains displaying differences in µ opioid-induced tolerance and physical dependence: C56BL/6J, 129P3/J, SJL/J and SWR/J. The complete mRNA expression profiles of the OPRM1 splice variants reveal marked differences of the variant mRNA expression among the brain regions in each mouse strain, suggesting region-specific alternative splicing of the OPRM1 gene. The expression of many variants was also strain-specific, implying a genetic influence on OPRM1 alternative splicing. The expression levels of a number of the variant mRNAs in certain brain regions appear to correlate with strain sensitivities to morphine analgesia, tolerance and physical dependence in four mouse strains.

摘要

μ阿片受体基因(OPRM1)在啮齿动物和人类中经历广泛的前体mRNA可变剪接,产生数十种OPRM1基因的可变剪接变体。本研究建立了一种SYBR Green定量PCR(qPCR)检测方法,以更准确地定量小鼠OPRM1剪接变体mRNA。使用这些qPCR检测方法,我们检测了四种近交系小鼠品系(C56BL/6J、129P3/J、SJL/J和SWR/J)在μ阿片诱导的耐受性和身体依赖性方面存在差异的特定脑区中OPRM1剪接变体mRNA的表达。OPRM1剪接变体的完整mRNA表达谱显示,每个小鼠品系的脑区之间变体mRNA表达存在显著差异,表明OPRM1基因存在区域特异性可变剪接。许多变体的表达也是品系特异性的,这意味着对OPRM1可变剪接存在遗传影响。某些脑区中一些变体mRNA的表达水平似乎与四种小鼠品系对吗啡镇痛、耐受性和身体依赖性的品系敏感性相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7f/4208855/d7b1f7c6d388/pone.0111267.g001.jpg

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