Animal Models & Phenotyping Core

D.摘要(动物模型和表型核心) 在过去的10年里(Y1-5和Y6-10的资助)，动物模型和表型的任务 核心(AMPC)是为了制造高质量的转基因和基因敲除小鼠的生产和代谢 NORC成员无论在技术上还是在经济上都很容易获得行为表型。《野兽》 模型和表型核心(AMPC)由两个交互组件组成：动物模型 亚核与能量代谢和行为亚核。AMPC提供的服务结合了 体内代谢表型和基因表达调控技术的研究进展 详细的行为分析。在过去的两个供资周期(Y1-5和Y6-10)中，APMC一直是一个关键 彭宁顿国家海洋和大气研究中心的总体任务的组成部分，其任务是鼓励与 营养与肥胖。核心目标如下：目标1：利用转基因和基因打靶 产生模拟人类疾病状态的小鼠模型的技术，如肥胖和胰岛素 抵抗力，当暴露在肥胖环境(久坐的生活方式和高热量饮食)中时。目标2： 进行详细的体内代谢表型鉴定，以评估生理功能的指标，如能量 支出、脂肪积累、食物摄入量和新陈代谢灵活性。目标3：进行体内实验 对动物行为进行详细分析，以支持NORC成员和试点和可行性计划。 目标4：根据NORC成员的观察，寻求新的方法和实验范式 中试和可行性试验。上述目标将使用遗传和其他因素的组合来实现 在活体内接近。在实验中可以改变基因构成来研究特定的作用 肥胖和糖尿病的基因不能在人类身上执行。这些研究将确定 作用于代谢功能障碍的进展(即胰岛素抵抗、异位脂肪沉积、代谢 不灵活，胰腺功能障碍等)通过使用发展成肥胖和胰岛素抵抗的啮齿动物模型 通过直接的基因操作或接触高脂肪饮食。因此，通过严格的体内代谢 结合NORC调查人员对相关组织的详细机制分析，表型分析， AMPC帮助NORC的所有项目解决了一个关键的悬而未决的问题，即一个肥胖的环境如何 在全身水平影响正常新陈代谢。

D. Abstract (Animal Models & Phenotyping Core) During the past 10 years (Y1-5 and Y6-10 of funding), the mandate of the Animal Models and Phenotyping Core (AMPC) was to make high quality transgenic and gene knockout mouse production and metabolic and behavioral phenotyping readily accessible, both technically and financially, to NORC members. The Animal Models and Phenotyping Core (AMPC) is comprised of two interactive components: the Animal Models Subcore and the Energy Metabolism and Behavioral Subcore. THE AMPC provides services that combined controlled manipulation of gene expression in mice with state-of-the-art in vivo metabolic phenotyping and detailed behavioral analysis. Over the past two funding cycles (Y1-5, Y6-10), the APMC has been a key component of the overall mission of the Pennington NORC to stimulate new and innovative research related to nutrition and obesity. The aims of the core are as follows: Aim 1: To utilize transgenic and gene targeting techniques to generate mouse models that mimic human disease states, such as obesity and insulin resistance, when exposed to an obeseogenic environment (sedentary lifestyle and high caloric diets). Aim 2: To conduct detailed in vivo metabolic phenotyping to assess measures of physiologic function such as, energy expenditure, fat accumulation, food intake, and metabolic flexibility. Aim 3: Conduct in vivo experiments for detailed analysis of animal behavior so as to support NORC members and the Pilot and Feasibility Program. Aim 4: Pursue new methods and experimental paradigms based on observations from NORC members and Pilot and Feasibility experiments. The above Aims will be performed using a combination of genetic and other in vivo approaches. Experiments in which the genetic constitution can be changed to study the role of specific genes on obesity and diabetes cannot be performed in humans. These studies will identify mechanisms that act on the progression of metabolic dysfunction (i.e., insulin resistance, ectopic fat deposition, metabolic inflexibility, pancreatic dysfunction, etc) by using rodent models that develop obesity and insulin resistance through direct genetic manipulation or exposure to high fat diets. Thus, through rigorous in vivo metabolic phenotyping in conjunction with detailed mechanistic analysis of relevant tissues by NORC investigators, the AMPC helps all NORC projects address the critical unanswered question of how an obesogenic environment affects normal metabolism at the whole body level.