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用于研究遗传因素对人类戒烟成功因素影响的小鼠模型。

Mouse models for studying genetic influences on factors determining smoking cessation success in humans.

机构信息

Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, Maryland 21224, USA.

出版信息

Ann N Y Acad Sci. 2012 Feb;1248:39-70. doi: 10.1111/j.1749-6632.2011.06415.x.

Abstract

Humans differ in their ability to quit using addictive substances, including nicotine, the major psychoactive ingredient in tobacco. For tobacco smoking, a substantial body of evidence, largely derived from twin studies, indicates that approximately half of these individual differences in ability to quit are heritable genetic influences that likely overlap with those for other addictive substances. Both twin and molecular genetic studies support overlapping influences on nicotine addiction vulnerability and smoking cessation success, although there is little formal analysis of the twin data that support this important point. None of the current datasets provides clarity concerning which heritable factors might provide robust dimensions around which individuals differ in ability to quit smoking. One approach to this problem is to test mice with genetic variations in genes that contain human variants that alter quit success. This review considers which features of quit success should be included in a comprehensive approach to elucidate the genetics of quit success, and how those features may be modeled in mice.

摘要

人类在戒除成瘾物质(包括尼古丁,烟草中的主要精神活性成分)的能力上存在差异。对于吸烟行为,大量证据主要来自于双胞胎研究,表明在这些个体差异中,大约有一半是可遗传的基因影响,这可能与其他成瘾物质的影响重叠。双胞胎和分子遗传学研究都支持尼古丁成瘾易感性和戒烟成功的重叠影响,尽管很少有对双胞胎数据的正式分析来支持这一重要观点。目前没有任何数据集能够清楚地说明哪些可遗传因素可能为个体在戒烟能力上的差异提供稳健的维度。解决这个问题的一种方法是测试携带人类变体的基因发生遗传变异的老鼠,这些变体改变了戒烟的成功率。这篇综述考虑了应该将哪些戒烟成功的特征纳入到阐明戒烟成功的遗传学的综合方法中,以及这些特征如何在老鼠中进行建模。

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