The National Center for Metabolic Phenotyping of Mouse Models of Obesity and Diabetes (MPMOD) at UC Davis

国家肥胖和糖尿病活体模型代谢表型研究中心 加州大学戴维斯分校 摘要--总体部分 根据疾病控制中心的数据，超过三分之一的美国成年人患有肥胖症， 并发症(如心脏病、中风、癌症)，每年给美国经济造成的损失超过1500亿美元。 事实还不止于此：美国疾病控制与预防中心最近的数据显示，2型糖尿病的发病率正在上升， 达到了今天美国成年人口的11%左右。遗传学、环境因素、食物和 体力活动行为、慢性应激和同时发生的高危疾病都指向糖尿病和肥胖。 是异源起源的疾病。在此背景下，先进的研究更好地综合表型 为了充分了解疾病的发病机制，尤其需要与人类状况相关的小鼠模型 以及为遏制这一不断上升的流行病的战略提供信息的机制。 利用遗传、外科、人源化和其他类型的小鼠模型进行体内翻译研究 现在尤其需要用来描述疾病的发病机制、机制和后果。这些型号 需要与人类代谢性疾病的病理生理学相关，以便更有效地告知 诊断、治疗和预防策略。促进这一努力并加快实现这些目标的进展 Goals，加州大学戴维斯分校提议建立一个国家新陈代谢表型中心 肥胖和糖尿病(MPMOD)。该中心将为糖尿病和肥胖症研究社区提供 访问专业和高级资源，以评估采用独特、复杂和 难找的测试和程序。MPMOD用户还将连接到有能力、有经验和 就实验设计、测试选择、结果测量和解释提供专家咨询和建议。 加州大学戴维斯分校MPMOD团队为研究社区提供了坚实的服务基础：过去10年 多年来，加州大学戴维斯分校担任NIDDK代谢小鼠表型中心(MMPC)的旗舰 财团，提供活体小鼠服务，并对小鼠组织和血浆进行体外分析 为更大的研究社区提供血清。加州大学戴维斯分校的MPMOD中心将在这些成功的基础上 和我们强大的基础设施，提供许多新颖和创新的方法来解决生活中的新问题 MICE，利用加州大学戴维斯分校更大的科学企业和核心实验室提供研究社区 通过体内高质量的代谢、生理和行为表型服务来表征 糖尿病、肥胖症和相关代谢紊乱的异质性、发病机制和后果。 加州大学戴维斯分校的MPMOD中心将由一个行政核心组成，提供行政、服务、 和对该中心的业务监督；一个动物核心，将进口和提供畜牧、护理和 许多特殊服务(例如，SPF畜牧业、灵知生物鼠管理、ABSL3条件、 提交给该中心的小鼠的显微手术能力、尸检和组织病理学)；代谢和 代谢健康核心，拥有丰富的资源和专业知识，提供完善的代谢表型分析 测试加上创新的方法(例如，PET成像、连续血糖监测、尖端能量 平衡措施，异种代谢组学)，以揭示大量营养素代谢、能量摄入和 摄食行为、能量消耗和代谢效率；以及具有 具备相当广度和深度的专门知识和能力，以深入评估器官和 全动物生理学(心血管、胃肠、肾脏、呼吸系统、眼科和神经科)和 运动行为、睡眠、学习和记忆、焦虑、抑郁和 压力以及与糖尿病和肥胖症相关的运动功能。每个核心都将有一名科学领袖和 共同领导、核心协调员和技术专家进行实验。无数的科学 附属于每个核心的顾问将提供关于实验设计、测试 选择和数据解释，并应要求提供新颖和复杂的测试和程序。 除了全面的测试和咨询外，加州大学戴维斯分校MPMOD中心的主要优势 将与国际公认的资产密切合作，生产和分享新型鼠标 疾病模型。科学家当然可以送他们自己的老鼠去测试，但除此之外，他们还可以订购一种 糖尿病或肥胖的小鼠模型(例如，加州大学戴维斯分校的MMRRC、KOMP2程序)或 该中心为他们制作了一个相关的从头开始的小鼠模型(例如，基因改变的减肥手术模型)。 将以合理的价格向所有将获得同等服务优先级的用户提供服务，无论 加州大学戴维斯分校内部或外部机构。该中心将把项目收入再投资于开发新的测试 技术，资助合作项目，支持减免费用，资助试点和可行性研究。这个 中心有意通过参与Shared成为MPMOD联盟的积极和积极的成员 管理国家MPMOD计划，并提供补充服务，以避免昂贵和 其他MPMOD中心之间的重叠效率低下。最后，该中心将积极参与 并提出了MPMOD中心和MPMOD中心之间的创新合作伙伴关系 由23个校区组成的加州州立大学(CSU)系统中的西班牙裔服务机构(HSI)。

National Center for Metabolic Phenotyping in Live Models of Obesity and Diabetes (MPMOD) at UC Davis ABSTRACT—OVERALL SECTION According to the Centers for Disease Control, more than a third of U.S. adults are obese, suffer related complications (e.g., heart disease, stroke, cancer), and cost the US economy more than $150 billion annually. And the facts don’t stop there: recent data from the CDC reveal an increasing incidence of type 2 diabetes, reaching a prevalence of ~11% of the US adult population today. Genetics, environmental factors, food and physical activity behaviors, chronic stress, and coincident high-risk morbidities all point to diabetes and obesity being diseases of heterogenic origin. In this context, advanced research to comprehensively phenotype better mouse models relevant to the human condition is especially needed to fully understand disease pathogenesis and mechanisms to inform strategies for curbing this rising epidemic. Translational research in vivo using genetic, surgical, humanized, and other types of mouse models are needed especially now to characterize disease pathogenesis, mechanisms, and consequences. These models need to be relevant to the pathophysiology of human metabolic disease so as to inform more effective diagnostic, therapeutic, and prevention strategies. To catalyze this effort and accelerate progress toward these goals, UC Davis proposes the creation of a National Center for Metabolic Phenotyping of Mouse Models of Obesity and Diabetes (MPMOD). The Center will provide the diabetes and obesity research communities access to specialized and advanced resources to assess mouse models employing unique, complex, and hard-to-find tests and procedures. MPMOD users will also be connected to competent, experienced, and expert consultation and advice on experimental design, test selection, outcomes measures, and interpretation. The UC Davis MPMOD team has a solid foundation of service to the research community: for the last 10 years, UC Davis served as a flagship in the NIDDK Metabolic Mouse Phenotyping Center (MMPC) Consortium, providing in vivo services on live mice and in vitro analyses on murine tissue and plasma and serum to the greater research community. The MPMOD Center at UC Davis will build from those successes and our strong infrastructure to offer many novel and innovative approaches to tackle new questions in live mice, drawing upon the larger UC Davis scientific enterprise and core labs to provide the research community with high quality metabolic, physiologic, and behavioral phenotyping services in vivo to characterize the heterogeneity, pathogenesis, and consequences of diabetes, obesity, and related metabolic disorders. The MPMOD Center at UC Davis will consist of an Administrative Core providing administrative, service, and business oversight for the Center; an Animal Core that will import and provide husbandry, care, and numerous special services (e.g., SPF husbandry, gnotobiotic mouse management, ABSL3 conditions, microsurgery capability, necropsy and histopathology) for mice submitted to the Center; a Metabolism and Metabolic Health Core with significant resources and expertise to offer well-established metabolic phenotyping tests plus innovative approaches (e.g., PET imaging, continuous glucose monitoring, sophisticated energy balance measures, xenometabolomics) to reveal subtle shifts in macronutrient metabolism, energy intake and feeding behaviors, energy expenditure and metabolic efficiency; and a Physiology and Behavior Core with substantial breadth and depth of expertise and capabilities to provide in-depth assessments of organ and whole-animal physiology (cardiovascular, gastrointestinal, renal, respiratory, ocular, and neurological) and neurobehavioral assessment of exercise behavior, sleep, learning and memory, anxiety, depression and stress, and motor function relevant to diabetes and obesity. Each of the Cores will have a Scientific Leader and co-Leader, Core Coordinator, and Technical Specialists to conduct experiments. Numerous Scientific Consultants affiliated with each Core will be available to offer expert advice on experimental design, test selection, and data interpretation, and provide novel and complex tests and procedures upon request. In addition to comprehensive tests and consultation, a major strength of the MPMOD Center at UC Davis will be a close association with internationally recognized assets for production and sharing of novel mouse disease models. Scientists can of course send in their own mice for testing, but in addition they can order a mouse model of diabetes or obesity from a repository (e.g., the UC Davis MMRRC, KOMP2 programs) or have the Center make a relevant mouse model de novo (e.g., genetically-altered, bariatric surgery model) for them. Services will be offered at reasonable cost to all users who will be afforded equal service priority whether from inside UC Davis or an outside institution. The Center will reinvest program income to develop new testing technologies, fund collaborative projects, support fee waivers, and subsidize pilot and feasibility studies. The Center intends to be an active and engaged member of the MPMOD Consortium by participating in shared governance of the national MPMOD Program and by providing complementary services to avoid costly and inefficient overlap between other MPMOD Centers. Finally, the Center will be an active participant in the MPMOD Vibrant Program and has proposed an innovative partnership between MPMOD Centers and Hispanic Serving Institutions (HSIs) in the 23-campus California State University (CSU) system.