The genomic determinants of alcohol preference in mice
The genomic determinants of alcohol preference in mice
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DOI：
10.1007/s00335-008-9115-z
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发表时间：
2008-05-01
期刊：
影响因子：
2.5
通讯作者：
Hoffman, Paula L.
中科院分区：
文献类型：
--
作者：
Tabakoff, Boris;Saba, Laura;Hoffman, Paula L.
对影响人类和其他动物饮酒水平的基因的识别常常是由特定基因产物在确定乙醇的积极或消极增强作用方面的重要性的预设所驱动的。我们采取了一种公正的方法，对三种类型的小鼠群体进行了荟萃分析，将大脑基因表达与酒精摄入水平联系起来。我们的研究使用基于 QTL 分析的过滤程序，产生了八个具有高度遗传表达的候选基因的列表，这可以解释小鼠酒精偏好的显着差异。使用艾伦脑图谱进行基因表达，我们注意到候选基因的表达定位于嗅觉和边缘区域以及眶额皮质。信息学技术和通路分析说明了候选基因在神经元迁移、分化和突触重塑中的作用。讨论了嗅觉线索、学习和记忆形成（巴甫洛夫条件反射）以及皮质执行功能对于调节动物（包括人类）酒精摄入量的重要性。
Searches for the identity of genes that influence the levels of alcohol consumption by humans and other animals have often been driven by presupposition of the importance of particular gene products in determining positively or negatively reinforcing effects of ethanol. We have taken an unbiased approach and performed a meta-analysis across three types of mouse populations to correlate brain gene expression with levels of alcohol intake. Our studies, using filtering procedures based on QTL analysis, produced a list of eight candidate genes with highly heritable expression, which could explain a significant amount of the variance in alcohol preference in mice. Using the Allen Brain Atlas for gene expression, we noted that the candidate genes' expression was localized to the olfactory and limbic areas as well as to the orbitofrontal cortex. Informatics techniques and pathway analysis illustrated the role of the candidate genes in neuronal migration, differentiation, and synaptic remodeling. The importance of olfactory cues, learning and memory formation (Pavlovian conditioning), and cortical executive function, for regulating alcohol intake by animals (including humans), is discussed.