Michigan Mouse Metabolic Phenotyping Center

密歇根小鼠代谢表型中心

• 批准号: 9174673
• 负责人: MALCOLM James LOW
• 金额: $ 116.11万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-02 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9174673
• 关键词: Accounting; Animals; Area; Atherosclerosis; Award; Behavior; Biochemical; Bioinformatics; Biological; Biological Assay; Biological Models; Blindness; Blood Pressure; Blood Vessels; Cardiac; Cardiovascular Physiology; Cardiovascular system; Caring; Clinical Chemistry; Collaborations; Complications of Diabetes Mellitus; Culex (Genus); Data; Data Set; Databases; Development; Diabetes Mellitus; Diabetic Angiopathies; Diet; Disease; Echocardiography; Educational workshop; Electrocardiogram; Endocrine; Euglycemic Clamping; Exercise Tolerance; Fostering; Functional disorder; Funding; Gastrectomy; Generations; Genes; Genomics; Germ-Free; Glucose; Glucose Clamp; Gnotobiotic; Goals; Grant; Health Care Costs; Healthcare; Heart failure; Histopathology; Homeostasis; Hormones; Housing; Human; Image; In Vitro; Indirect Calorimetry; Institution; Kidney Diseases; Kidney Failure; Laboratories; Leadership; Libraries; Liquid substance; Literature; Maintenance; Measurement; Metabolic; Metabolic Diseases; Metabolism; Michigan; Microvascular Dysfunction; Modeling; Motor Activity; Mouse Strains; Mus; Myocardial Ischemia; Nerve; Neuropathy; Obesity; Operant Conditioning; Pathogenesis; Pattern; Phenotype; Physiological; Physiology; Protocols documentation; Publishing; Reproducibility; Research; Research Personnel; Resources; Retinal Diseases; Rewards; Ribosomal RNA; Sampling; Sensitivity and Specificity; Services; Surgical Models; Telemetry; Testing; Tissues; Training Programs; Ultrasonography; Universities; Wild Type Mouse; abstracting; animal care; bariatric surgery; behavior measurement; biobehavior; blood glucose regulation; burden of illness; cost; diabetic; experience; glucose tolerance; gut microbiome; in vivo; insulin tolerance; knowledge base; macrovascular disease; medical schools; member; metabolic phenotype; microbial; microbial genome; microbiome; mouse model; novel; operation; pressure; programs; tool; training opportunity; transcriptome sequencing; transcriptomics; transmission process

Project Summary / Abstract – 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.

项目概要/摘要-总体 代谢紊乱及其血管并发症是最紧迫的医疗保健问题之一 国际吧密歇根大学医学院战略性地投资于人类和身体 在过去的15年里，在密歇根综合糖尿病中心的保护下， 对这一问题的共同攻击。该战略的一个组成部分是促进发展核心 大学内的实验室以合理的价格提供关键的专业知识和专业的表型分析服务。 整个机构的研究人员的成本。我们现在建议合并这些表型的四个 核心到密歇根州MMPC继续提供全面的和最先进的服务， 同时在国家一级扩大对研究人员的可用性，并继续开发更多的 敏感和更具体的工具来探测糖尿病的发病机制和生化后果， 肥胖小鼠模型。密歇根MMPC将在四个主要领域提供服务。新陈代谢， 减肥手术和行为核心将进行各种体内生理评估，包括 葡萄糖稳态（葡萄糖耐量、胰岛素耐量、高胰岛素血症/正常血糖钳夹）、能量 稳态（CLAMS间接测热法，饮食挑战），超日激素分泌（Culex平台 对于来自不受约束的小鼠的连续生物流体取样），行为测量（自发活动，进餐 模式分析、操作性条件反射）和减肥手术模型的产生。心血管 病理生理学核心将评估心血管功能（运动耐量、血压、ECG、遥测， 超声心动图），提供心脏缺血和压力超负荷的小鼠手术模型，并使用 超声.微血管并发症核心将提供糖尿病的基本和高级评估 并发症包括神经病变、肾病和视网膜病变。微生物组核心将提供 厌氧微生物培养，微生物组基因组和转录组文库，16 S核糖体基因和RNA 测序与相关的生物信息学分析。小鼠进口、圈养、兽医护理、临床 化学和组织病理学服务将由动物护理中心提供。此外，后者的核心 拥有一个无菌小鼠设施，并将与微生物组核心互动，以生产和分发无菌 和无菌小鼠模型。行政核心将管理所有中心活动，监督财务 操作，提供培训机会，并与其他表型中心和中央 MMPC联盟的协调和生物信息学单位，提供所有收集的表型数据， 协议，并参与试点和可行性奖和MICROMouse资助计划。在一起， 我们的核心资源将在一个中心提供广泛的先进表型分析 能力，包括我们对微血管并发症、微生物组分析的独特关注和专业知识 以及无菌小鼠和减肥手术模型。