Mouse Genetic Models for Alcohol Research

描述(由申请者提供)：我们为酒精研究保留了大量独特的小鼠基因类型。这些动物被用于由多个R01、U01、波特兰酒精研究中心(PARC)P60拨款和几个VA功绩审查补助金支持的研究。这些动物已经被波特兰、俄勒冈州和世界各地的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是在使用它们的主要赠款的预算中编制的，但成本膨胀以及赠款周期和实际使用之间缺乏同步导致我们越来越落后于我们支持这些小鼠的能力。我们之所以能够跟上这一趋势，部分原因是通货膨胀超过了NIH可乐的限制，部分原因是几项主要支持拨款(P60、UOIs和VA Merit Review)的预算上限。拟议的R24寻求适度的支持，以保持这些基因类型，在每种情况下，费用与使用费和来自父母赠款的维护支持分担。目标1.帮助维持长期选择的品系及其遗传异质性控制系(WSP-1、WSP-2、WSR-1、WSR-2、FAST-1、FAST-2、Slow-1、Slow-2、WSC、HDID-1、HDID-2和HS/NPT)的核心育种群体。目的2.为数量性状座位(QTL)基因定位研究维持同源品系和自交系及其祖先近交系的核心育种群体(覆盖第1、6、19染色体部分区域的17个基因类型及其祖先近交系C57BL/6J(86)和DBA/2J(D2)，以及覆盖第1和11染色体上的QTL的两个基因类型iWSP2、IWSR-1)。目的3.帮助维持遗传异质性群体HS-CC的核心育种群体，该群体由复杂性状联盟衍生，用于高级杂交QTL定位研究。目的4.部分支付长期选择品系和同源菌株的超低温保存费用。冷冻保存可防止关键基因的灾难性丢失，并为未来的使用提供了可能[HOT-1、HOT-2、COLD-1、COLD-2、WSP-1、WSP-2、WSR-1、WSR-2、HDID-1、HDID-2，以及染色体1、4、11和19上的22个同源菌株(5个待冷冻保存)]。感兴趣的研究人员可以免费获得所涵盖的所有基因类型。没有申请支持分配的资金，因为这种支持是在支持各种基因类型的主要赠款项下提供的。支持繁殖和测试额外动物的资金也不是这里要求的，而是根据父母的赠款。 相关性：遗传动物模型，特别是小鼠和大鼠的遗传动物模型，一直是我们理解酒精使用障碍的病理生理学的主要贡献。可用于小鼠的遗传学和基因组学资源使该物种在确定遗传风险和开发新的药物疗法方面特别有价值。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.