Scripps Genetic Animal Models Core Component

斯克里普斯遗传动物模型核心组件

• 批准号: 6449657
• 负责人: AMANDA J ROBERTS
• 金额: $ 20.54万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6449657
• 关键词: alcoholic beverage consumption; animal breeding; animal colony; biomedical facility; ethanol; gene environment interaction; gene targeting; genetic models; genetically modified animals; genotype; laboratory mouse; model design /development; mutant; phenotype; self medication

DESCRIPTION (provided by applicant): The overall Genetic Animal Models Core (GAMC) will be overseen by Dr. John Crabbe, Professor of Behavioral Neuroscience, Oregon Health Sciences University (OHSU). The major goal of the GAMC is to integrate animal model development, availability and usage across sites. It will facilitate the development of more robust phenotypes and genotypes; facilitate the exploration of gene by 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 INIA sites and Cores: and to provide relevant data to the Informatics Core. The Scripps Research Institute Animal Models Core Component will be primarily focused on developing more robust phenotypes and genotypes of excessive ethanol consumption. For example, a model of excessive ethanol drinking in dependent mice following periods of protracted abstinence will be developed and optimized. Mice will be trained to self-administer ethanol in an operant procedure, made dependent using an ethanol liquid diet and then allowed access to ethanol self-administration again following period of protracted abstinence. It is hypothesized that subacute withdrawal syndrome persists for weeks to months in rodents (years in humans) and may be associated with excessive or uncontrolled ethanol drinking behavior. IN addition, several mouse models available through Scripps Research Institute collaborations will be maintained and investigated in terms of ethanol self-administration in both non-dependent and dependent states. These include the corticotropin releasing factor (CRF) receptor 1 (R1) and receptor 2 (R2) knockout mice and the mu and delta opioid receptor knockout mice. These strains will be made available on a pure C57BL/6 background. Site specific mu and delta opioid receptor knockout mice with mutations targeted to extended amygdala circuitry will also become available (Kieffer, developmental U01). In addition, several mouse lines conditionally over expressing transcription factors will be investigators within this Core Component. Once characterized, these strains will become available throughout INIA for molecular, cellular and circuitry analyses.

描述（由申请人提供）： 整个遗传动物模型核心 (GAMC) 将由 John 博士监督 Crabbe，俄勒冈健康科学行为神经科学教授 大学（OHSU）。 GAMC的主要目标是整合动物模型 跨站点的开发、可用性和使用。它将有利于 开发更强大的表型和基因型；促进 通过环境相互作用探索基因并促进发展 新颖的基因技术来探索两次打击假设，即至少 两组基因必须失调才能产生滥用性的自我管理； 实现遗传动物模型的协调利用和 跨 INIA 站点和核心的开发：并向 信息学核心。斯克里普斯研究所动物模型核心组件 将主要致力于开发更强大的表型和基因型 过量的乙醇消耗。例如，过量乙醇的模型 长期禁酒后，依赖小鼠饮酒将 开发和优化。小鼠将接受训练以自我施用乙醇 一种手术程序，使用乙醇流质饮食进行依赖，然后 允许在一段时间后再次进行乙醇自我管理 长期禁欲。据推测，亚急性戒断综合征 在啮齿动物中持续数周至数月（在人类中持续数年），并且可能 与过量或不受控制的乙醇饮用行为有关。在 此外，斯克里普斯研究所提供了几种小鼠模型 将在乙醇自我管理方面保持和研究合作 在非依赖和依赖状态下。这些包括 促肾上腺皮质激素释放因子 (CRF) 受体 1 (R1) 和受体 2 (R2) 基因敲除小鼠和 mu 和 delta 阿片受体基因敲除小鼠。这些 菌株将在纯 C57BL/6 背景下提供。场地特定亩 和 δ 阿片受体基因敲除小鼠，其突变靶向延长 杏仁核电路也将可用（Kieffer，发育中的 U01）。 此外，一些小鼠品系有条件地过度表达转录 因素将是该核心组件内的调查员。一旦表征， 这些菌株将在整个 INIA 中用于分子、细胞 和电路分析。