GENETIC APPROACHES TO NEUROPHARMACOLOGY OF ETHANOL

这份申请是为了继续科罗拉多大学的 研究中心。这个中心从NIAAA起就正式存在了 CENTERS计划于1977年启动。该中心的总体目标是 定义决定初始状态的机制(遗传和功能) 对酒精中毒的敏感性和对酒精的耐受性 这些影响。该中心是从动物模型开发和 特征化到特定基因识别的水平。 我们将利用现有的遗传敏感性模型并开发 对乙醇耐受性的新方法。中心调查人员将继续 对特定行为使用选择性繁殖技术，但将 也强调基于基因类型选择的新模式(同源系) 以及单基因(转基因和零突变小鼠)的变化。确实有 分离和鉴定QTL中特定基因的建议 敏感度。我们将继续提供我们独特的动物模型 世界各地其他机构的调查人员。这些遗传模型 将被用来定义生化和电生理机制 对所选行为负责，并提供有关 可能导致这些功能变化的候选基因。在……里面 此外，还将使用分子遗传学方法来阐明 负责行为、生化和性别差异的基因序列 QTL分析鉴定出电生理差异。这 多学科方法提供广泛的互动和协同 在项目之间。 这一目标将通过六个研究组成部分来实现，一个动物 生产核心、行政核心和四个试点。

This application is to continue the University of Colorado Alcohol Research Center. This center has been in formal existence since the NIAAA Centers program was initiated in 1977. The overall goal of this Center is to define the mechanisms (genetic and functional) that determine initial sensitivity to alcohol intoxication and the development of tolerance to these effects. The Center has evolved from animal model development and characterization to the level of specific gene identification. We will utilize existing models for genetic sensitivity and develop new ones for tolerance to ethanol. Center investigators will continue to use the technique of selective breeding for specific behaviors but will also emphasize new models based on genotypic selection (congenic lines) and changes in single genes (transgenic and null mutant mice). There are proposals to isolate and identify specific genes within QTLs for initial sensitivity. We will continue to provide our unique animal models to investigators at other institutions around the world. These genetic models will be used to define the biochemical and electrophysiological mechanisms responsible for the selected behavior and to provide information about candidate genes that may be responsible for these functional changes. In addition, molecular genetic approaches will be used to elucidate differences in gene sequences responsible for behavioral, biochemical, and electrophysiological differences identified by QTL analysis. This multidisciplinary approach provides extensive interaction and synergism between projects. This goals will be accomplished by six research components, an animal production core, and administrative core, and four pilot projects.