Mouse Genetic Models for Alcohol Research

描述（由申请人提供）：我们保留了大量独特的基因型小鼠用于酒精研究。这些动物被用于多个R 01，U 01，波特兰酒精研究中心（PARC）P60补助金和几个VA Merit Review赠款支持的研究。这些动物已经被波特兰、俄勒冈州和世界各地许多其他地点的研究人员用于研究。对所有这些基因型的部分支持都在使用它们的主要赠款中进行了预算，但是成本膨胀以及补助金周期和实际使用之间缺乏同步性导致我们越来越落后于我们支持这些小鼠的能力。我们能够跟上的部分原因是通货膨胀超过了NIH COLA的限制，部分原因是几个主要支持赠款（P60，UOI和VA Merit Reviews）的预算上限。拟议的R24寻求适度的支持，以维持这些基因型，在每种情况下，与用户费用和父母赠款的维持支持分摊成本。有四个目标：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、FAST-1、FAST-2、SLOW-1、SLOW-2、WSC、HDID-1、HDID-2和HS/Npt）的核心育种菌落。目标2.帮助维持同源品系和品系及其祖先近交系的核心育种群体，用于数量性状位点（QTL）基因定位研究（17种基因型，覆盖1号、6号和19号染色体的部分区域及其祖先近交系，C57 BL/6 J（86）和DBA /2 J（D2），以及两种基因型，覆盖1号和11号染色体上的QTL，iWSP 2、iWSR-1）。目标3.帮助维持遗传异质性股票HS-CC的核心育种菌落，由复杂性状联盟为先进的互交QTL定位研究。目标4。部分支付长期选择品系和同类品系的冷冻保存费用。冷冻保存可防止关键基因型的灾难性损失，并为潜在的未来使用提供途径[HOT-1、HOT-2、COLD-1、COLD-2、WSP-1、WSP-2、WSR-1、WSR-2、HDID-1、HDID-2和22个同源菌株（5个待冷冻保存），用于染色体1、4、11和19上的数量性状基因座]。所涵盖的所有基因型都免费提供给感兴趣的研究人员。不需要资金来支持分发，因为这种支持是在支持各种基因型的基本赠款下提供的。这里也不要求提供资金来支持额外动物的繁殖和测试，而是在父母赠款下提供。 相关性：遗传动物模型，特别是小鼠和大鼠，是我们理解酒精使用障碍病理生理学的主要贡献者。可用于小鼠的遗传学和基因组学资源使得该物种对于确定遗传风险和开发新的药物疗法特别有价值。我们寻求支持的模式是独一无二的。

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, the Portland Alcohol Research Center (PARC) P60 grant, 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 all these genotypes is budgeted within the primary grants employing them, but cost inflation and the lack of synchrony between grant cycles and actual use has led us to fall further and further behind our ability to support these mice. Our ability to 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, UOIs, and VA Merit Reviews). The proposed R24 seeks modest support to maintain these 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, FAST-1, FAST-2, SLOW-1, SLOW-2, WSC, HDID-1, HDID-2, and HS/Npt). Aim 2. Help maintain core breeding colonies of congenic strains and lines, and their progenitor inbred strains, for quantitative trait locus (QTL) gene mapping studies (17 genotypes covering parts of chromosomes 1, 6, and 19 and their progenitor inbred strains, C57BL/6J (86) and DBA /2J (D2), and two genotypes covering QTLs on chromosomes 1 and 11, iWSP2, iWSR-1). Aim 3. Help maintain core breeding colonies for the genetically heterogeneous stock HS-CC, derived by the Complex Trait Consortium for advanced intercross QTL mapping studies. Aim 4. Partially defray costs for cryopreservation of long term selected lines and congenic strains. Cryopreservation protects against catastrophic loss of crucial genotypes as well as providing access for potential future use [HOT-1, HOT-2, COLD-1, COLD-2, WSP-1, WSP-2, WSR-1, WSR-2, HDID-1, HDID-2, and 22 congenic strains (5 to be cryopreserved) for quantitative trait loci on chromosomes 1,4, 11 and 19]. All genotypes covered are freely available to interested investigators at cost. 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. RELEVANCE: Genetic animal models, particularly with mice and rats, have been major contributors to our understanding of the pathophysiology of alcohol use disorders. The genetics and genomics resources available for mouse makes this species especially valuable for ascertaining genetic risk and developing novel pharmacotherapies. The models for which we seek support are unique.