? Overall Metabolic disorders and their vascular complications are among the most pressing healthcare issues worldwide. The University of Michigan Medical School has strategically invested in both human and physical resources over the past 15 years under the umbrella of the Michigan Comprehensive Diabetes Center in a concerted attack on this problem. One component of the strategy has been to foster the development of core laboratories within the university to provide key expertise and specialized phenotyping services at reasonable cost to researchers throughout the institution. We now propose to coalesce a quartet of these phenotyping cores into the Michigan MMPC to continue providing comprehensive and state of the art services internally, while expanding their availability to researchers on a national level, and continuing the development of more sensitive and more specific tools to probe the pathogenesis and biochemical consequences of diabetes and obesity in mouse models. The Michigan MMPC will provide services in four major areas. The Metabolism, Bariatric Surgery and Behavior Core will perform a variety of in vivo physiological assessments encompassing glucose homeostasis (glucose tolerance, insulin tolerance, hyperinsulinemic/euglycemic clamps), energy homeostasis (indirect calorimetry by CLAMS, dietary challenge), ultradian hormone secretion (Culex platform for serial biological fluid sampling from unrestrained mice), behavioral measurements (locomotor activity, meal pattern analysis, operant conditioning) and generation of bariatric surgery models. The Cardiovascular Pathophysiology Core will assess cardiovascular function (exercise tolerance, blood pressure, ECG, telemetry, echocardiogram), offer mouse surgical models of cardiac ischemia and pressure overload and imaging using ultrasound. The Microvascular Complications Core will provide basic and advanced assessment of diabetes complications including neuropathy, nephropathy, and retinopathy. The Microbiome Core will provide anaerobic microbial culture, microbiome genomic and transcriptomic libraries, 16S ribosomal gene and RNA sequencing with associated bioinformatic analysis. Mouse importation, housing, veterinary care, clinical chemistry and histopathology services will be provided by the Animal Care Core. In addition, the latter core hosts a germ-free mouse facility and will interact with the Microbiome core to produce and distribute germ-free and gnotobiotic mouse models. The Administrative Core will manage all Center activities, oversee financial operations, provide training opportunities, and collaborate with the other phenotyping centers and the Central Coordinating and Bioinformatics Unit of the MMPC Consortium by providing all collected phenotyping data and protocols and participating in the Pilot and Feasibility award and MICROMouse funding programs. Together, our Core resources will provide in a single Center access to a broad range of advanced phenotyping capabilities, including our unique focus and expertise on microvascular complications, microbiome analysis and germ-free mice and bariatric surgery models.
? Overall Diabetes, obesity, and associated macrovascular and microvascular complications including atherosclerosis, nerve damage, kidney failure and blindness account for a major share of disease burden and health care costs nationwide. The proposed Michigan Mouse Metabolic Phenotyping Center will provide researchers access to advanced phenotyping services including whole animal physiology, cardiac pathophysiology, microvascular complications, and microbiome analysis to investigate the pathophysiology and development of novel treatments for these disorders using mouse model systems.
