Mouse Models of Alcohol Induced Behavior

描述(由申请人提供)： 50多年前首次进行的许多研究表明，基因在调节人类酒精中毒的发展过程中发挥着重要作用。不幸的是，在实际识别导致酒精中毒的基因方面进展有限。在这方面，动物模型可能会有一些用处。在科罗拉多大学和其他地方进行的许多研究表明，基因控制着许多酒精诱导和相关的行为。我们早期的大部分工作都致力于确定基因是否影响酒精表型。其中一个特别成功的领域是长睡眠(LS)和短睡眠(SS)小鼠品系的发展。这些品系是从近交系、异种系(HS)小鼠开始的选择性育种而来的。近年来，我们一直在寻找调节睡眠时间表型的基因。从LS和SS小鼠中培育出同源品系和重组近交系品系，这将在识别调节睡眠时间表型的基因方面非常有用。也许更重要的是，这些小鼠已经被证明在研究许多其他酒精表型方面有价值。我们还通过从HS种群中进行选择性育种，培育出了不同于急性功能耐受(首剂耐受)的小鼠品系(Haft-Laft)。这些老鼠是一种非常宝贵和独特的资源，必须加以维护。提交这份R24申请是为了确保科罗拉多大学的酒精遗传学研究继续取得成功，这样我们就可以继续向其他研究人员提供我们有价值的动物。

DESCRIPTION (provided by applicant): Many studies, the first done more than 50 years ago, have demonstrated that genes play an important role in regulating the development of alcoholism in humans. Unfortunately, only limited progress has been made towards actually identifying genes that contribute to alcoholism. Animal models may be of some utility in this respect. Many studies done at the University of Colorado, as well as other places, have demonstrated that genes regulate many alcohol-induced and-related behaviors. Much of our early work was devoted to determining whether genes influence alcohol phenotypes. One area of particular success was the development of the long-sleep (LS) and short-sleep (SS) mouse lines. These lines were derived by selective breeding starting from the outbred, heterogeneous stock (HS) mice. In recent years we have been searching for the genes that regulate the sleep time phenotype. Congenic strains and recombinant inbred strains have been developed from the LS and SS mice that will be very useful in identifying genes that regulate the sleep time phenotype. Perhaps of greater importance, these mice have already proven to be of value in studying many other alcohol phenotypes. We have also developed mouse lines (HAFT-LAFT) that differ from acute functional tolerance (first dose tolerance) to alcohol, via selective breeding from the HS stock. These mice are a very valuable and unique resource that must be maintained. This R24 application is being submitted to help guarantee the continued success of alcohol genetics research at the University of Colorado and so that we can continue to supply our valuable animals to other researchers.