GENETIC STUDIES OF GABA RECEPTOR FUNCTION

我们中心的一个目标是确定抑制性神经元的作用 系统和受体在酒精敏感性方面的遗传差异。这 研究方向从我们的集体工作中产生，显示出差异 LS和SS小鼠在GABAA受体上的差异。在这个项目中，我们建议 通过询问以下五个主要项目中的任何一个来链接和扩展ARC正在进行的研究 乙醇敏感性QTL决定GABAA基因的功能差异 感受器。这种方法将利用组件3中的同源小鼠 GABAA受体功能的生化研究。 此外，我们还将重点介绍伽马的两个变体的作用 体内和体外酒精敏感性中的GABAA受体亚单位。 这些研究将基于过度表达该基因的转基因小鼠 Gamma2S或Gamma2L亚基。这些转基因的影响将被评估 在不同的遗传背景上，包括129SvevTac，C57BL/6J， ILS和ISS.这些MICE也将被提供给 弧形。

One goal of our Center is to determine the role of inhibitory neuronal systems and receptors in genetic differences in alcohol sensitivity. This research direction has arisen from our collective work showing differences between LS and SS mice in GABAa receptors. In this project, we propose to link and extend ongoing studies in the ARC by asking if any of five major QTLs for ethanol sensitivity determine functional differences in GABAa receptors. This approach will utilize congenic mice from component 3 for biochemical studies of GABAa receptor function. In addition, we will focus on the roles of the two variants of the gamma subunit of the GABAa receptor in alcohol sensitivity in vivo and in vitro. These studies will be based on transgenic mice that overexpress either the gamma2S or gamma2L subunit. Effects of these transgenes will be evaluated on several different genetic backgrounds including 129SvevTac, C57BL/6J, ILS, and ISS. These mice will also be provided to other projects in the ARC.