Mouse Genetic Models for Alcohol Research

描述（由申请人提供）：我们拥有大量独特基因型的小鼠用于酒精研究。这些动物被用于由多个r01、u01、波特兰酒精研究中心（PARC） P60资助和几项VA Merit Review资助支持的研究。这些动物被俄勒冈州波特兰市和世界上许多其他地方的研究人员用于研究。对所有这些基因型的部分支持在使用它们的主要赠款中进行了预算，但成本膨胀以及赠款周期与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。我们能够保持这种能力部分是由于通货膨胀超过了NIH COLA的限制，部分是由于几个主要支持拨款的预算上限（P60， uis和VA Merit Reviews）。拟议的R24寻求适度支持以维持这些基因型，在每种情况下，费用由用户费用和来自亲本赠款的维持支持分担。有四个目标：帮助维持长期选择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。目标2。帮助维持同源菌株和系及其祖先自交系的核心育种菌落，用于数量性状位点（QTL）基因定位研究（17个基因型覆盖1、6和19号染色体及其祖先自交系C57BL/6J（86）和DBA /2J （D2）部分，2个基因型覆盖1和11号染色体iWSP2， iWSR-1的QTL）。目标3。帮助维持由复杂性状联盟为高级交叉QTL定位研究衍生的遗传异质性种群HS-CC的核心育种菌落。目标4。部分支付长期选择品系和同源品系冷冻保存的费用。低温保存可以防止关键基因型的灾难性丢失，并为潜在的未来使用提供了途径[HOT-1， HOT-2, COLD-1, COLD-2, WSP-1, WSR-1, WSR-2, HDID-1， HDID-2和22个同源菌株（5个被低温保存）用于染色体1,4,11和19上的数量性状位点]。所涵盖的所有基因型都是免费提供给感兴趣的研究者的。没有要求为支持分发提供资金，因为这种支持是在支持各种基因型的主要赠款下提供的。支持其他动物的繁殖和试验的资金也没有在这里要求，而是在父母赠款下。

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.