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

描述（由申请人提供）：本申请申请资金用于升级和扩展具有环境控制的综合实验动物监测系统（CLAMS），这将显著加速研究和发现，特别是在包括肥胖、2型糖尿病和非酒精性脂肪性肝病在内的常见代谢紊乱方面。CLAMS被用于不受约束、有意识的小鼠的间接量热，产生定量测量氧气消耗（VO2）、二氧化碳产生（VCO2）、呼吸交换比（底物利用的指标）、总能量消耗和体温。它还提供了基础运动活动和运动耐受性以及热量摄入的措施。我们现有的蛤蜊是专门的，允许精确控制环境温度范围从热中性（30℃）到冷（4℃）。这一特征对于系统地量化产热是必不可少的，产热是指从储存的能量中产生体热的能力。控制产热的机制有望成为治疗肥胖和糖尿病的靶点，但人们对其了解甚少。在我们的初步研究中，CLAMS的使用揭示了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在代谢研究中的应用有浓厚的兴趣。我们现有的CLAMS设备一次只允许研究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，并且在计划和执行协议方面存在困难。拟议的扩展将允许我们每次实验监测多达24只老鼠。这种能力将在可获得的蛤蜊应急系统和对其使用的需求之间取得适当的平衡。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效率。

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.