Vanderbilt O'Brien Kidney Center-Core A Physiology-Pathiophysiology Core

范德比尔特奥布莱恩肾脏中心-核心生理学-病理生理学核心

• 批准号: 9385113
• 负责人: Mingzhi Zhang
• 金额: $ 31.6万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9385113
• 关键词: Acute; Address; Adverse drug effect; Animals; Bioenergetics; CRISPR/Cas technology; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Complement; Education; Ethylnitrosourea; Experimental Models; Functional disorder; Gene Delivery; Generations; Genes; Genetic; Genome; Image Analysis; Imaging Techniques; Immunologics; Immunotherapy; Information Dissemination; Injury; International; Intervention; Kidney; Kidney Diseases; Kidney Function Tests; Mass Spectrum Analysis; Measurement; Metabolic; Metabolism; Methodology; Methods; Modeling; Mus; Mutant Strains Mice; Mutation; Oxygen; Oxygen Consumption; Pathogenesis; Pharmacologic Substance; Phenotype; Physiology; Pilot Projects; Renal function; Reproducibility of Results; Research; Research Infrastructure; Research Personnel; Resources; Services; Structure; TNFSF5 gene; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Training; Venous; base; blood flow measurement; cost effective; design; design and construction; drug testing; glucose uptake; in vivo; insight; interest; investigator training; kidney imaging; mouse model; mutant; new technology; non-invasive imaging; novel; overexpression; prevent; programs; screening; tool

ABSTRACT The Phenotyping and Pathophysiology Core is designed to address the need for effective phenotyping of kidney function in mouse models of selective gene overexpression or deletion. In addition, this Core is designed to provide experimental mouse models of acute or progressive renal injury to assess potential therapeutic interventions. This Core also helps investigators who may have developed genetic mouse models or potential therapeutic interventions but do not have the expertise and/or infrastructure required to design and carry out appropriate kidney phenotyping studies or studies investigating mouse models of kidney injury. In this proposal, we propose five distinct subcores that will offer and/or develop methodologies to define the pathogenesis of kidney disease and design therapeutic interventions. The Phenotyping Subcore will provide a battery of well-established invasive and non-invasive tests of kidney function. The Injury Model Subcore will provide investigators cost-effective testing of potential pharmaceutical or immunologic therapy strategies in appropriate mouse models of acute or progressive kidney injury. In addition, this subcore will provide murine models for screening of potential kidney side effects of drugs. This subcore provides a wide variety of experimental models of mouse kidney injury that offer consistent and reproducible results. Some of the mouse models available have been developed by the Center investigators. The Metabolism and Bioenergetics Subcore will offer direct measurements of kidney tissue partial oxygen consumption and will develop methodology for the measurements of whole kidney oxygen consumption based on kidney blood flow and measurements of arterial and renal venous partial oxygen. Furthermore this subcore will provide expertise in metabolic flux analysis, glucose uptake and quantification of various metabolites in kidney tissues using mass spectrometry methods. The Mouse Kidney Imaging Subcore will provide established non-invasive imaging techniques for the assessments of mouse renal diseases and will provide methods and further optimize novel methods for the noninvasive characterization of renal microstructure and function in mice. The CRISPR/cas9 Subcore will provide guidance for the design, construction, and generation of a CRISPR mouse. In summary, the Phenotyping and Pathophysiology Core provides a broad range of services that aid researchers interested in utilizing murine models for kidney-related research. The structure of this Core is unique in that it performs a variety of kidney functions, non-invasive quantitative kidney images analysis, and experimental platforms for the testing of drugs and interventions. Importantly, this Core performs all these services in house and directly oversees these studies. We have been very successful in providing these services not only to the local scientific community interested in kidney research, but also in serving as a national and international resource.

摘要 表型和病理生理学核心是为了满足对有效的表型的需求 小鼠肾功能选择性基因过度表达或缺失模型。此外，这个核心是 旨在提供急性或进行性肾损伤的实验性小鼠模型，以评估其潜力 治疗性干预。这个核心还帮助可能已经开发出遗传老鼠模型的研究人员 或潜在的治疗干预措施，但不具备设计和 进行适当的肾脏表型研究或研究肾脏损伤的小鼠模型。在这 提案中，我们提出了五个不同的子核，它们将提供和/或开发定义 肾脏疾病的发病机制和设计治疗干预措施。表型亚核将提供 一系列成熟的侵入性和非侵入性肾功能测试。伤害模型亚核将 为研究人员提供具有成本效益的潜在药物或免疫治疗策略测试 建立合适的急性或进行性肾损伤小鼠模型。此外，这个亚核将为小鼠提供 筛选药物潜在肾脏副作用的模型。这个子核提供了各种各样的 提供一致和可重复性结果的小鼠肾脏损伤的实验模型。一些老鼠 现有的模型已经由该中心的调查人员开发出来。代谢与生物能量学 亚核将提供肾组织部分耗氧量的直接测量，并将开发 基于肾脏血流量和血流量的全肾耗氧量测量方法 测量动脉和肾静脉的部分氧含量。此外，该分核心将在以下方面提供专门知识 利用质量分析肾组织代谢通量、葡萄糖摄取和各种代谢物的定量 光谱分析方法。小鼠肾脏成像亚核将提供已建立的非侵入性成像 将为小鼠肾脏疾病的评估提供方法和进一步优化新技术 小鼠肾脏微结构和功能的无创性表征方法。CRISPR/CAS9 Subcore将为CRISPR鼠标的设计、建造和生成提供指导。 总而言之，表型和病理生理学核心提供了广泛的服务，帮助 有兴趣利用小鼠模型进行肾脏相关研究的研究人员。这个核心的结构是 其独特之处在于，它可以执行各种肾脏功能、非侵入性量化肾脏图像分析以及 药物和干预试验的实验平台。重要的是，这个核心执行所有这些 内部服务，并直接监督这些研究。我们已经非常成功地提供了这些 不仅服务于对肾脏研究感兴趣的当地科学界，而且还服务于 国家和国际资源。