Mouse Genetic Models for Alcohol Excessive Drinking and Dependence

酒精过度饮酒和依赖的小鼠遗传模型

• 批准号: 9072359
• 负责人: JOHN C. CRABBE
• 金额: $ 23.14万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-05 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9072359
• 关键词: ARHGEF5 gene; Adult; Age; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Animal Model; Animal Testing; Animals; Breathing; Breeding; Budgets; Chromosome Mapping; Chromosomes, Human, Pair 1; Congenic Strain; Cost Sharing; Cryopreservation; Dependence; Economic Inflation; Ethanol; Evolution; Fees; Funding; Future; GIRK3 subunit, G protein-coupled inwardly-rectifying potassium channel; Genes; Genetic; Genetic Models; Genotype; Grant; Grant Review; Heavy Drinking; Individual; Institutes; Knock-out; Maintenance; Monoclonal Antibody R24; Mus; Oregon; Pharmaceutical Preparations; Phenotype; Physical Dependence; Postdoctoral Fellow; Quantitative Trait Loci; Research; Research Design; Research Personnel; Research Project Grants; Research Support; Resistance; Rewards; Risk; Seizures; Site; Source; Students; Testing; Therapeutic Intervention; Tissues; Transgenic Organisms; United States National Institutes of Health; Withdrawal; alcohol research; alcohol use disorder; career development; congenic; cost; drinking; falls; genetic makeup; human subject; interest; mouse model; nonhuman primate; parent grant; public health relevance; research study; vapor

 DESCRIPTION (provided by applicant): We maintain a large number of unique genotypes of mice for alcohol research studies. These animals are used in research supported by multiple R01s, U01s, and several VA Merit Review Grants. These animals have been used for research by investigators in Portland, Oregon and at many other sites around the world. Partial support for these genotypes has come from the Portland Alcohol Research Center (PARC) P60 grant, Dr. Crabbe's VA Merit Review grant, and has been budgeted within the primary grants employing them. Cost inflation and the lack of synchrony between grant cycles and actual use has led us to fall further and further behind in our ability to support these mice. Our inability t keep up is due partly to inflation exceeding the NIH COLA limits, and partly to budget caps on several of the principal supporting grants (P60, U01s, and VA Merit Reviews). Furthermore, the PARC P60 grant will no longer be using these genotypes when it renews Jan 1 2016, so this source of cost-sharing will be lost. The proposed R24 seeks modest support to maintain multiple genotypes, in each case cost-shared with user fees and maintenance support from the parent grants. There are four aims: Aim 1. Help maintain core breeding colonies of long-term selected lines and their genetically heterogeneous control lines (WSP-1, WSP-2, WSR-1, WSR-2, WSC, HDID-1, HDID-2, and HS/Npt). Aim 2. Help maintain core breeding colonies of congenic strains and lines and transgenic or knockout strains, for quantitative trait locus (QTL) gene mapping studies. Aim 3. Partially defray costs for cryopreservation of long term selected lines and congenic and transgenic strains. Cryopreservation protects against catastrophic loss of crucial genotypes as well as providing access for potential future use [selected lines WSP-1, WSP-2, WSR-1, WSR-2, HDID-1, HDID-2, and the knockout B6.GIRK3-/-]. Aim 4. Partially defray costs of maintaining an ethanol vapor inhalation core for producing physical dependence. This core supports multiple grants and investigators. Cost-sharing from the PARC P60 grant will no longer be available as PARC studies in the renewal will not employ physical dependence. All genotypes covered are made available to interested investigators. Funds to support distribution are not requested, as this support is provided under the primary grants supporting the various genotypes. Funds to support breeding and testing of additional animals are also not requested here, but rather under the parent grants.

 描述（由申请人提供）：我们保留了大量用于酒精研究的独特基因型小鼠，这些动物用于由多个 R01、U01 和多项 VA 优异评审资助支持的研究。俄勒冈州波特兰和世界各地许多其他地点的研究人员对这些基因型的部分支持来自波特兰酒精研究中心 (PARC) P60 拨款、Crabbe 博士的 VA 优异评审拨款，并已获得批准。成本通胀以及拨款周期与实际使用之间缺乏同步性导致我们支持这些小鼠的能力越来越落后，部分原因是通货膨胀超过了预算。 NIH COLA 限制，部分是对几个主要支持拨款（P60、U01s 和 VA Merit Reviews）的预算上限。此外，PARC P60 拨款在 1 月 1 日续订时将不再使用这些基因型2016 年，因此这种费用分摊来源将消失。拟议的 R24 寻求适度的支持来维持多种基因型，在每种情况下都与用户费用和家长补助金的维护支持分摊。目标 1. 帮助。维持长期选择品系及其遗传异质对照品系（WSP-1、WSP-2、WSR-1、WSR-2、WSC、HDID-1、HDID-2 和目标 2. 帮助维持同源品系和品系以及转基因或敲除品系的核心育种群体，以进行数量性状基因座 (QTL) 基因定位研究。 目标 3. 部分支付长期选定品系和同源品系的冷冻保存费用。和转基因菌株可以防止关键基因型的灾难性损失，并为未来的潜在使用提供途径[选定的品系 WSP-1、WSP-2、 WSR-1、WSR-2、HDID-1、HDID-2 和敲除 B6.GIRK3-/-] 目标 4. 部分支付维持乙醇蒸气吸入核心以产生身体依赖性的费用 该核心支持多项资助。 PARC P60 补助金的费用分摊将不再适用，因为更新中的 PARC 研究将不再采用身体依赖性，所有基因型都将提供给感兴趣的研究人员以支持分配。不需要，因为这种支持是在支持各种基因型的主要赠款下提供的，这里也没有要求支持其他动物的育种和测试，而是在父赠款下。