GENETIC APPROACHES TO NEUROPHARMACOLOGY OF ETHANOL

此申请是为了继续科罗拉多大学的酒精 研究中心该中心自NIAAA以来一直正式存在 中心计划于1977年启动。本中心的总体目标是 定义决定初始基因的机制（遗传和功能） 对酒精中毒的敏感性和对酒精的耐受性的发展 这些影响。该中心从动物模型发展演变而来， 特征鉴定到特定基因鉴定的水平。 我们将利用现有的遗传敏感性模型， 对乙醇的耐受性。研究人员将继续 对特定的行为使用选择性繁殖的技术， 还强调基于基因型选择的新模式（同源系） 和单基因的变化（转基因和无效突变小鼠）。有 建议分离和鉴定QTL内的特定基因， 灵敏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研究人员。这些基因模型 将用于定义生物化学和电生理机制 对所选行为负责，并提供有关 这些候选基因可能是导致这些功能变化的原因。在 此外，分子遗传学方法将用于阐明 基因序列的差异，负责行为，生化， 通过QTL分析鉴定电生理差异。这 多学科方法提供了广泛的互动和协同作用 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项目。

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.