Integrated system for phenotyping energy balance and metabolism in animal models

用于动物模型能量平衡和代谢表型分析的集成系统

• 批准号: 7795396
• 负责人: DANIEL POMP
• 金额: $ 44.47万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-06 至 2011-05-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795396
• 关键词: Advisory Committees; Animal Behavior; Animal Model; Animals; Atherosclerosis; Back; Biological; Body fat; Carbon Dioxide; Charge; Clinical Nutrition; Collection; Complex; Consumption; Core Facility; Data; Diabetes Mellitus; Disease; Disease model; Energy Intake; Energy Metabolism; Environment; Equipment; Evaluation; Exercise; Food; Food Preferences; Funding; Genetic; Genetic Medicine; Genotype; Goals; Home environment; Housing; Imagery; Inbred Mouse; Indirect Calorimetry; Individual; Investigation; Liquid substance; Malignant Neoplasms; Measurement; Mental disorders; Metabolic; Metabolism; Mus; Nutritional Study; Obesity; Online Systems; Pattern; Phenotype; Play; Population; Production; Randomized; Recombinants; Research; Research Personnel; Research Support; Reservations; Resources; Role; Services; Stress; System; Time; Variant; bone mass; drinking; drinking behavior; energy balance; experience; feeding; genome-wide; instrumentation; knockout gene; mouse model; respiratory; tool; trait

DESCRIPTION (provided by applicant): Energy balance, the relationship between energy consumed (through food and drink) and energy expended (through activity and metabolic rate), plays a central role in many diseases, including obesity, diabetes, atherosclerosis, certain cancers and some psychiatric disorders, among others. Mouse models, in various forms such as individual gene knockouts and large, segregating polygenic populations, play a central role in understanding energy balance as a complex trait, including genetic and environmental underpinnings and their interactions. Our long-term objective is to facilitate multifaceted use of mouse models to study energy balance by supporting high quality and high throughput phenotyping of energy balance components, including energy intake, food preference, metabolic rate, home cage activity, voluntary exercise, and serial measurements of body fat, lean mass and bone. Towards this goal, we created an Animal Metabolism Phenotyping (AMP) core facility in 2005 within the NIH-funded Clinical Nutrition Research Center (CNRC) at UNC, and have been providing energy balance phenotyping services to a broad array of NIH-funded biomedical researchers. Our current aim is to significantly expand and upgrade our phenotyping capabilities by placing into the AMP core an integrated 32-cage LabMaster CaloSys (TSE Systems) platform. This includes measurement of indirect calorimetry (O2 consumption & CO2 production, respiratory exchange rate, energy expenditure), feeding and drinking behavior (including amounts and time patterns, food preference, and control of food/liquid access), and spontaneous home cage activity. This system uses the home-cage environment for unbiased stress-free animal behavior, and greatly increases our capabilities to facilitate and support research on a wide variety of diseases that have underpinnings in disregulated energy balance. Thus, use of the requested instrumentation can play a central role in synergizing investigations of many important disease models around one of their important core and common causes. Equipment in the AMP core will be housed in dedicated space within the Vivarium of UNC's new Genetic Medicine Research Building, with capacity for ~45,000 mouse cages. Usage will focus primarily on investigation of a unique new complex trait disease mouse model housed at UNC, the Collaborative Cross (CC), and on evaluation of the consequences of gene knockouts. The CC is a very large panel of recombinant inbred mouse lines and is the only mammalian resource that has high and uniform genome-wide variation effectively randomized across a large, heterogeneous, and reproducible population which also supports integration across environmental and biological conditions, across genotypes, and over time. Equipment use will be streamlined through the experienced CNRC Administrative Core, providing web-based reservations, centralized charge-back billing, and oversight by internal and external advisory committees. Tools developed by UNC's Computational Genetics Group will be used for collection, visualization and dissemination of data.

描述（由申请人提供）：能量平衡，即能量消耗（通过食物和饮料）与能量消耗（通过活动和代谢率）之间的关系，在许多疾病中发挥着核心作用，包括肥胖、糖尿病、动脉粥样硬化、某些癌症和一些精神疾病等等。小鼠模型以各种形式（例如个体基因敲除和大型分离多基因群体）在理解能量平衡作为一种复杂性状（包括遗传和环境基础及其相互作用）方面发挥着核心作用。我们的长期目标是通过支持能量平衡组成部分的高质量和高通量表型分析，包括能量摄入、食物偏好、代谢率、笼内活动、自愿运动和系列测量，促进多方面使用小鼠模型来研究能量平衡身体脂肪、去脂体重和骨骼。为了实现这一目标，我们于 2005 年在 NIH 资助的北卡罗来纳大学临床营养研究中心 (CNRC) 内创建了动物代谢表型 (AMP) 核心设施，并一直为 NIH 资助的众多生物医学研究人员提供能量平衡表型服务。我们当前的目标是通过在 AMP 核心中放置一个集成的 32 笼 LabMaster CaloSys (TSE Systems) 平台来显着扩展和升级我们的表型分析能力。这包括间接热量测定（氧气消耗和二氧化碳产生、呼吸交换率、能量消耗）、进食和饮水行为（包括数量和时间模式、食物偏好以及食物/液体获取控制）以及自发的笼内活动的测量。该系统利用家笼环境实现公正、无压力的动物行为，并极大地提高了我们促进和支持对以能量平衡失调为基础的各种疾病的研究的能力。因此，使用所需的仪器可以在围绕其重要核心和常见原因之一的许多重要疾病模型的协同研究中发挥核心作用。 AMP 核心的设备将安置在北卡罗来纳大学新遗传医学研究大楼动物园内的专用空间内，可容纳约 45,000 个小鼠笼子。用途将主要集中于对北卡罗来纳大学协作交叉（CC）中独特的新型复杂性状疾病小鼠模型的研究，以及对基因敲除后果的评估。 CC 是一个非常大的重组近交系小鼠品系，是唯一具有高度一致的全基因组变异的哺乳动物资源，该变异在大型、异质且可重复的群体中有效随机化，同时也支持跨环境和生物条件、跨基因型的整合，并且随着时间的推移。设备的使用将通过经验丰富的 CNRC 管理核心进行简化，提供基于网络的预订、集中退款计费以及内部和外部咨询委员会的监督。北卡罗来纳大学计算遗传学小组开发的工具将用于数据的收集、可视化和传播。