The alpha 3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation.
The alpha 3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation.
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DOI：
10.1111/j.1601-183x.2008.00444.x
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Phillips TJ
中科院分区：
文献类型：
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作者：
Kamens HM;McKinnon CS;Li N;Helms ML;Belknap JK;Phillips TJ
酒精和尼古丁是共同滥用的，临床前和临床数据表明，共同的基因可能会影响对这两种药物的反应。在小鼠9号染色体的一个区域中，包括一簇三个烟碱乙酰胆碱受体（nAChR）亚基基因的基因影响对乙醇的运动刺激反应。目前的研究首先使用同源小鼠来确认9号染色体上的影响基因。然后使用同类F2小鼠更精细地绘制位置。在对乙醇反应不同的小鼠品系中，对三个亚基基因的基因表达进行定量。最后，在α3 nAChR亚基基因（Chrna 3）无效突变杂合子小鼠中检查了对乙醇的运动反应。同源数据表明，9号染色体上的一个基因，在一个46 cM的区域内，包含集群的nAChR亚基基因，占41%的遗传变异的刺激响应乙醇。与受到强烈刺激的小鼠相比，在对乙醇诱导的刺激不太敏感的小鼠中，在与运动行为相关的全脑和解剖脑区域中发现了更多的Chrna 3表达;基因簇中的其他两个nAChR亚基基因（α5和β4）没有差异表达。Chrna 3杂合（+/-）和野生型（+/+）小鼠的遗传背景上不表达运动刺激; +/-小鼠比+/+小鼠对乙醇的运动抑制作用更敏感。chrna 3是一个候选基因的急性运动刺激反应，乙醇，值得进一步研究。
Alcohol and nicotine are coabused, and preclinical and clinical data suggest that common genes may influence responses to both drugs. A gene in a region of mouse chromosome 9 that includes a cluster of three nicotinic acetylcholine receptor (nAChR) subunit genes influences the locomotor stimulant response to ethanol. The current studies first used congenic mice to confirm the influential gene on chromosome 9. Congenic F2 mice were then used to more finely map the location. Gene expression of the three subunit genes was quantified in strains of mice that differ in response to ethanol. Finally, the locomotor response to ethanol was examined in mice heterozygous for a null mutation of the α3 nAChR subunit gene (Chrna3). Congenic data indicate that a gene on chromosome 9, within a 46 cM region that contains the cluster of nAChR subunit genes, accounts for 41% of the genetic variation in the stimulant response to ethanol. Greater expression of Chrna3 was found in whole brain and dissected brain regions relevant to locomotor behavior in mice that were less sensitive to ethanol-induced stimulation compared to mice that were robustly stimulated; the other two nAChR subunit genes in the gene cluster (α5 and β4) were not differentially expressed. Locomotor stimulation was not expressed on the genetic background of Chrna3 heterozygous (+/−) and wild-type (+/+) mice; +/− mice were more sensitive than +/+ mice to the locomotor depressant effects of ethanol. Chrna3 is a candidate gene for the acute locomotor stimulant response to ethanol that deserves further examination.