INIA: ANIMAL CORE

描述(由申请人提供)： 由于所维护的遗传动物模型之间的差异，使用 并在6个IMA站点中的5个站点开发，支持单独的U-24应用程序 每个站点都在提交遗传动物模型。约翰·克拉布博士， 俄勒冈健康科学大学行为神经科学教授 (OHSU)，将担任整个遗传动物模型核心的协调人 在本申请中描述的。GAMC的主要目标是整合 动物模型开发、可获得性和跨站点使用。遗传动物 自第一次酒精研究以来，模特一直是酒精研究的主要内容 它是在20世纪40年代末发展起来的，多年来人们已经知道动物 有酒精自我管理和/或酒精依赖的经验 在一段时间后的较短时间内增加其摄入量 戒烟。然而，这些和其他现有的模型还不是最优的。 一般来说，响应的大小和架构不会 令人信服地表现出严重的过度或明显的失控 在最初的醉人时期之后会持续很长时间 自治。实际上，人们对这种基因一无所知。 以上任何一项都增强了自我管理的倾向 操纵。几乎没有做过任何事情来描述这些特征 现有小鼠高、低酒精饮酒或饮酒遗传模型中的现象 高撤退或低撤退。GAMC的总体目标是促进 发展出更健壮的表型和基因类型；促进 探索X基因与环境的互作关系并促进其发展 探索两次命中假说的新基因技术，即至少 两组基因必须失控才能产生虐待 自我管理；实现遗传动物模型的协调利用 和跨IMA地点和核心的开发；并提供相关数据 信息学核心。在奥斯汀工地，特别强调的是 发展单基因缺失或突变的新型突变小鼠。 其他INIA项目所需的突变小鼠的构建将使用近交系 C57背景。突变小鼠将接受酒精表型测试 奥斯汀网站。

DESCRIPTION (provided by applicant): Due to the differences among the genetic animals models being maintained, used and developed in 5 of the 6 IMA sites, a separate U-24 application to support genetic animal models is being submitted from each site. Dr. John Crabbe, Professor of Behavioral Neuroscience, Oregon Health Sciences University (OHSU), will serve as coordinator of the overall Genetic Animal Models Core described in this application. The major goal of the GAMC is to integrate animal model development availability and usage across sites. Genetic animal models have been a major staple of alcohol research since the first were developed in the late 1940?s. it has been known for many years that animals experienced with alcohol self-administration and/or dependent on alcohol will increase their intake for a relatively short period of time after a period of withdrawal. However, these and other existing models are not yet optimal. Generally, the magnitude and architecture of the response does not convincingly display either gross excess or obvious loss of control that extends for a long time after the initial period of intoxicating self-administration. Virtually nothing is known about the genetic predisposition to self-administration potentiated by any of the above manipulations. Little to nothing has been done to characterize any of these phenomena in existing mouse genetic models of high or low ethanol drinking or high or low withdrawal. The general goals of the GAMC are to facilitate the development of more robust phenotypes and genotypes; facilitate the exploration of gene X environment interactions and facilitate development of novel genetic technology to explore the two-hit hypothesis, i.e. that at least two clusters of genes must be dysregulated to produce abusive self-administration; to achieve coordinated genetic animal model utilization and development across IMA sites and Cores; and to provide relevant data to the Informatics Core. At the Austin site, specific emphasis is placed on development of novel mutant mice with deletions or mutations of single genes. Construction of mutant mice required by other INIA projects will use an inbred C57 background. Mutant mice will be tested for alcohol phenotypes at the Austin site.