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Y 6 -10的资金），动物模型和表型分析的任务 核心（AMPC）是使高品质的转基因和基因敲除小鼠的生产和代谢， NORC成员在技术上和经济上都很容易获得行为表型分析。动物 模型和表型核心（AMPC）由两个交互式组件组成：动物模型 子核心和能量代谢和行为子核心。AMPC提供的服务结合了 用最先进的体内代谢表型对小鼠的基因表达进行控制操作， 详细的行为分析在过去的两个供资周期（Y1-5，Y 6 -10）中，APMC一直是 彭宁顿NORC的整体使命的一部分，以刺激新的和创新的研究有关， 营养和肥胖。本研究的主要目的如下：目的1：利用转基因技术和基因打靶技术 生成模拟人类疾病状态（例如肥胖和胰岛素）的小鼠模型的技术 抵抗力，当暴露于致肥胖环境（久坐的生活方式和高热量饮食）时。目标二： 进行详细的体内代谢表型分析，以评估生理功能指标，如能量 支出、脂肪积累、食物摄入和代谢灵活性。目的3：进行体内实验， 动物行为的详细分析，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， 试点和可行性实验。上述目标将使用遗传和其他方法相结合来实现。 in vivo体内approaches方法.可以改变遗传组成以研究特定基因作用的实验。 肥胖症和糖尿病的基因不能在人类身上进行。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 胰腺功能障碍等），通过使用发展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暴露于高脂肪饮食。因此，通过严格的体内代谢， NORC研究人员结合相关组织的表型分析和详细的机制分析， AMPC帮助所有NORC项目解决了一个关键的悬而未决的问题， 影响全身的正常新陈代谢。

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.