SELECTIVE BREEDING FOR ETHANOL SENSITIVITY

乙醇敏感性的选择性育种

• 批准号: 6783084
• 负责人: RICHARD A DEITRICH
• 金额: $ 34.19万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-18 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783084
• 关键词: GABA receptor; alcoholism /alcohol abuse; animal breeding; biological models; dehydroepiandrosterone; drug tolerance; ethanol; gene expression; genetic mapping; genetic susceptibility; genotype; glutamates; hormone receptor; laboratory rat; neurotensin; pharmacogenetics; phenotype; quantitative trait loci

DESCRIPTION (provided by applicant): Genetic risk for development of alcoholism in humans has been shown to be related to insensitivity to the initial effects of ethanol or to the development of acute tolerance to ethanol. This project utilizes rats that have been selectively bred for insensitivity or sensitivity to the initial effects of ethanol as a model of this phenomenon in humans. The project seeks to identify the genes responsible for this response in rats, to compare these results with similar studies in other rat selection studies and in mice to predict which genes may be responsible for the genetic risk factors in humans. The research utilizes methods of Quantitative Trait Loci (QTL) determination to locate these genes within the genome of the rat. Other breeding (development of congenic strains) and molecular biological methods are then used to focus on a narrower region of the genome in which these genes reside. This will allow the identification of the genes and show that they are responsible for a portion of the response to ethanol in the whole animal. This information is then applied to studies in humans to predict where genes will be found that influence the risk of development of alcoholism in humans. Development of prevention or treatment strategies will then be possible.

描述（由申请人提供）：人类酒精中毒的遗传风险已被证明与对乙醇的初始效应不敏感或对乙醇产生急性耐受性有关。该项目利用选择性饲养的对乙醇初始效应不敏感或敏感的大鼠作为人类这种现象的模型。该项目旨在确定导致大鼠这种反应的基因，并将这些结果与其他大鼠选择研究和小鼠的类似研究结果进行比较，以预测哪些基因可能导致人类的遗传风险因素。本研究利用定量性状位点（Quantitative Trait Loci， QTL）测定方法在大鼠基因组中定位这些基因。然后使用其他育种（同源菌株的开发）和分子生物学方法来关注这些基因所在的基因组的较窄区域。这将有助于识别基因，并表明它们对整个动物对乙醇的部分反应负责。然后将这些信息应用于人类研究，以预测在哪里可以发现影响人类酗酒风险的基因。这样就有可能制定预防或治疗策略。