Comprehensive Lab Animal Monitor System (CLAMS) for the Study of Mouse Metabolism

用于小鼠代谢研究的综合实验动物监测系统 (CLAMS)

• 批准号: 8826468
• 负责人: ALEXANDER BANKS
• 金额: $ 41.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-10 至 2016-02-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8826468
• 关键词: Animals; Body Temperature; Carbon Dioxide; Conscious; Diabetes Mellitus; Energy Intake; Energy Metabolism; Equilibrium; Exercise Tolerance; Funding; Heating; Indirect Calorimetry; Institution; Liver diseases; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Monitor; Motor Activity; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxygen Consumption; Production; Productivity; Protocols documentation; Request for Applications; Research; Research Personnel; Running; System; Technology; Temperature; Thermogenesis; Time; interest; mouse model; non-alcoholic fatty liver; obesity treatment; research study; respiratory

DESCRIPTION (provided by applicant): This application requests funds to upgrade and expand a Comprehensive Lab Animal Monitoring System (CLAMS) with environmental controls, which will markedly accelerate research and discovery, particularly in common metabolic disorders that include obesity, type 2 diabetes and non-alcoholic fatty liver disease. A CLAMS is utilized for indirect calorimetry of unrestrained, conscious mice, yielding quantitative measurements of oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio - an indicator of substrate utilization - total energy expenditure, and body temperature. It also provides measures of basal locomotor activity and exercise tolerance, as well as caloric intake. Our existing CLAMS is specialized, allowing for the precise control of ambient temperature ranging from thermoneutrality (30�C) to cold (4�C). This feature is essential for the systematic quantification of thermogenesis, the capacity to generate body heat from stored energy. Mechanisms that control thermogenesis hold great promise as targets for the treatment of obesity and diabetes, but are poorly understood. The use of a CLAMS in our initial studies has revealed profound changes in energy substrate utilization and induction of thermogenesis in multiple mouse models. As a result, there is keen interest among investigators at our institution to expand the use of CLAMS in their metabolic research. Our existing CLAMS facility allows for study of only 6 mice at a time (3 control, 3 experimental). Because each experiment typically lasts for 1-2 weeks, and requires duplicate runs to increase the number of mice monitored, this has created long waiting times and difficulty with the planning and execution of protocols. The proposed expansion will allow us to monitor up to 24 mice per experiment. This capacity will provide an appropriate balance between the availability of the CLAMS and the demand for its use. Because CLAMS is an absolutely essential technology for the understanding of mouse metabolism, the proposed expansion will fulfill a critical need and increase research productivity.

该申请要求资金用于升级和扩展具有环境控制的综合实验室动物监测系统（CLAMS），这将显著加速研究和发现，特别是在常见的代谢紊乱中，包括肥胖症，2型糖尿病和非酒精性脂肪肝疾病。CLAMS用于无限制的清醒小鼠的间接热量测定，产生耗氧量（VO 2）、二氧化碳产生量（VCO 2）、呼吸交换率（底物利用的指标）、总能量消耗和体温的定量测量。它还提供了基础自发活动和运动耐量以及热量摄入的测量。我们现有的CLAMS是专门的，允许精确控制环境温度，范围从热中性（30 ° C）到冷（4 ° C）。这一特征对于产热的系统量化是必不可少的，产热是从储存的能量产生身体热量的能力。控制产热的机制作为治疗肥胖和糖尿病的靶点有很大的希望，但了解甚少。在我们的初步研究中使用CLAMS揭示了在多种小鼠模型中能量底物利用和产热诱导的深刻变化。因此，我们机构的研究人员对扩大CLAMS在代谢研究中的使用非常感兴趣。我们现有的CLAMS设施允许一次仅研究6只小鼠（3只对照小鼠，3只实验小鼠）。由于每个实验通常持续1-2周，并且需要重复运行以增加监测的小鼠数量，这造成了漫长的等待时间以及方案规划和执行的困难。拟议的扩展将允许我们在每次实验中监测多达24只小鼠。这一能力将在CLAMS的可用性和使用需求之间提供适当的平衡。由于CLAMS是了解小鼠代谢的绝对必要技术，因此拟议的扩展将满足关键需求并提高研究生产力。