Integrated system for phenotyping energy balance and metabolism in animal models

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Abstract

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.