Animal & Resource Core

项目摘要 动物和资源核心（C 001）纳入本中心的更新反映了一个 一个研究企业，重点放在共享的遗传小鼠模型和集成的需求， 行为表型分析和高通量测序服务。为了满足这些要求，C 001将1） 建立和维持遗传小鼠模型的群体; 2）执行标准操作程序（SOP） 用于：基于乙醇偏好水平的短期选择性育种，通过两个- 瓶选择（2BC）程序，和认知灵活性的评价与设置转移程序;和3） 为RNA/DNA样品的提交和处理提供了一个简化的过程， 大规模并行测序共享资源（MPSSR）通过C 001的测序部门。集中 C 001中的这些角色和职责将减轻项目调查人员的开发负担， 独立的资源和程序，从而提供更大的自由，以解决有关 实验操作和执行尖端的分析，以解决特定的假设。动物& 资源核心计划将在整个中心范围内提供多种优势，包括降低研究成本 通过规模经济，提高科学严谨性和实验重现性， 畜牧和殖民地维护的做法，并实施优化的SOP由专门的工作人员在 恒定和受控的环境。C 001将与研究项目合作完成四个 具体目标。在目标1中，核心将建立、维护和分发遗传小鼠模型，以支持 中心研究项目。模型是异源原种协作杂交（HS-CC）小鼠， 选择性繁殖的高（HP）和低（LP）乙醇偏好的小鼠品系，和Aldh 111-EGFP-Rpl 10a 转基因小鼠在目标2中，核心将执行行为表型分析服务，包括那些SOP 这不仅适用于上文提到的，而且适用于有助于解释基因组和 对乙醇饮用的药理学操作，如味觉偏好、自发活动和乙醇 间隙在目标3中，将在HS-CC小鼠中优化一种设置转换程序，其与认知功能密切平行。 在恒河猴中进行的测试，从而增强了中心项目之间的跨物种翻译。 本SOP将用于在HP和LP小鼠中进行P001研究，以解决认知功能与 乙醇摄入以及P001和P004风险的灵活性，以解决以下剂量依赖性后果 慢性酒精摄入在目标4中，动物和资源核心的测序部门将执行下一个- 为所有研究项目提供一代测序服务，并将与生物信息学 Core（C 002）用于RNA-seq和全基因组DNAm-seq数据的比对和分析。

Project Summary The inclusion of an Animal & Resource Core (C001) in this Center renewal reflects the emergent needs of a research enterprise with an augmented focus on shared genetic mouse models and demands for integrated behavioral phenotyping and high-throughput sequencing services. To address these requirements, C001 will 1) establish and maintain colonies of genetic mouse models; 2) conduct standard operating procedures (SOPs) for: short-term selective breeding based on level of ethanol preference, chronic ethanol consumption via a two- bottle choice (2BC) procedure, and the evaluation of cognitive flexibility with a set-shifting procedure; and 3) provide a streamlined process for the submission and processing of RNA/DNA samples for sequencing by the Massively Parallel Sequencing Shared Resource (MPSSR) via the Sequencing Division of C001. Centralizing these roles and responsibilities within C001 will relieve project investigators from the burden of developing separate sets of resources and procedures, thereby providing greater latitude to address pertinent experimental manipulations and perform cutting-edge analyses to address specific hypotheses. Animal & Resource Core initiatives will offer multiple Center-wide advantages, including reduction of research costs through an economy of scale, enhanced scientific rigor and experimental reproducibility through standardized husbandry and colony maintenance practices, and implementation of optimized SOPs by dedicated staff in a constant and controlled environment. C001 will collaborate with the Research Projects in the completion of four Specific Aims. In Aim 1, the Core will establish, maintain and distribute genetic mouse models to support the Center Research Projects. The models are the Heterogeneous Stock Collaborative Cross (HS-CC) mice, selectively bred mouse lines for high (HP) and low (LP) ethanol preference, and Aldh1l1-EGFP-Rpl10a transgenic mice. In Aim 2, the Core will perform behavioral phenotyping services, including those SOPs mentioned above, but also for traits that aid in the interpretation of significant effects of genomic and pharmacological manipulations on ethanol drinking, such as tastant preference, locomotor activity, and ethanol clearance. In Aim 3, a set-shifting procedure will be optimized in HS-CC mice that closely parallels cognitive testing performed in rhesus macaques, thereby enhancing cross-species translation between Center projects. This SOP will be used to perform studies for P001 in HP and LP mice that address the relationship of cognitive flexibility with risk for ethanol intake and for P001 and P004 to address the dose-dependent consequences of chronic ethanol intake. In Aim 4, the Sequencing Division of the Animal & Resource Core will perform next- generation sequencing services for all Research Projects, and will work in conjunction with the Bioinformatics Core (C002) for the alignment and analysis of RNA-seq and genome-wide DNAm-seq data.