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

描述(申请人提供)：本申请申请资金，以升级和扩大具有环境控制的综合实验室动物监测系统(CLAMS)，这将显著加快研究和发现，特别是在常见的代谢疾病，包括肥胖、2型糖尿病和非酒精性脂肪性肝病。文蛤被用来间接测量自由、清醒的小鼠的热量，产生氧气消耗(VO2)、二氧化碳产生(VCO2)、呼吸交换率--底物利用的一个指标--总能量消耗和体温的定量测量。它还提供了基础运动活动和运动耐量以及卡路里摄入量的衡量标准。我们现有的文蛤是专门的，允许精确控制环境温度，范围从温度中和度(30�C)到冷温度(4�C)。这一特征对于系统量化生热作用是至关重要的，生热作用是指从储存的能量中产生身体热量的能力。控制生热的机制在肥胖症和糖尿病的治疗中大有希望，但人们对此知之甚少。在我们的初步研究中，使用文蛤在多个小鼠模型中显示了能量底物利用和产热诱导的深刻变化。因此，我们研究所的研究人员对扩大文蛤在代谢研究中的使用产生了浓厚的兴趣。我们现有的CLAMS设备一次只能研究6只小鼠(3只对照，3只实验)。由于每个实验通常持续1-2周，并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和计划和执行方案的困难。拟议的扩展将允许我们在每个实验中监控多达24只小鼠。这一能力将在文蛤的可获得性和使用需求之间提供适当的平衡。由于文蛤是了解老鼠新陈代谢的一项绝对必要的技术，拟议的扩展将满足一项关键需求，并提高研究生产率。

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.