INIA: ANIMAL CORE

描述（由申请人提供）： 由于遗传动物模型之间的差异， 并在6个IMA站点中的5个站点中开发了一个单独的U-24应用程序，以支持 每个地点都提交了遗传动物模型。约翰·克拉布博士， 俄勒冈州健康科学大学行为神经科学教授 （OHSU），将担任整体遗传动物模型核心的协调员 在本申请中描述。GAMC的主要目标是整合 动物模型开发的可用性和跨研究中心的使用。遗传动物 自从第一次出现以来，模型一直是酒精研究的主要内容。 在1940年末开发的？S.很多年前人们就知道 有酒精自我管理经验和/或依赖酒精的人 在一段时间后，在相对较短的时间内增加摄入量， 戒断然而，这些和其他现有的模型还不是最佳的。 一般来说，响应的幅度和结构并不 令人信服地显示严重过量或明显失控， 在最初的陶醉期之后持续很长一段时间， 自我管理。事实上，我们对遗传学一无所知。 由上述任何一种增强的自我管理倾向 操纵几乎没有做任何事情来描述这些 高或低乙醇饮用的现有小鼠遗传模型中的现象， 高或低的撤回。GAMC的总体目标是促进 发展更强大的表型和基因型;促进 探索X基因与环境的相互作用， 新的遗传技术来探索两次打击假设，即至少 必须有两组基因失调， 自我给药;实现协调的遗传动物模型利用 和开发;并提供相关数据， 信息学核心。在奥斯汀，特别强调的是 开发具有单个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小鼠。 C57背景。突变小鼠的酒精表型将在 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.