Animal Models Core

慢性肾脏疾病(CKD)与心血管疾病(CVD)的风险显著增加有关，因此CKD患者更有可能死于CVD而不是进展为终末期肾脏疾病。高血压(HTN)放大了心血管疾病的风险，影响着全球超过10亿人。然而，在大多数患者中，HTN的病因尚不确定，肾脏、HTN和心血管疾病之间复杂相互作用的机制以及随后的死亡风险尚不清楚。我们建议，对这些机制的准确定义将需要具有肾脏和心血管系统专业知识的多学科团队。因此，我们的目标是提供一组复杂的工具，以支持和促进在动物模型中关于肾脏、心血管疾病和HTN的独特联系的多学科基础发现研究。核心的配置是提供一系列肾脏、心脏和血管疾病的实验模型，核心人员在利用CKD、CVD和HTN的小鼠模型以及非哺乳动物模型的功能性肾脏和心血管筛查方面拥有全面的专业知识。核心将为肾脏或心血管研究人员提供服务，他们可能正在单独工作，以提高他们对心-肾轴的临床影响的认识，并提供获得模型和技术的途径，这些模型和技术可以吸引他们将他们的努力扩展到我们更广泛的主题兴趣领域。我们将为肾脏、血压等心血管功能提供全面的表型服务。核心的范围将是区域、国家和国际。核心工作人员将协助实验设计以及数据收集和分析。核心的能力还将有助于确定在肾脏基因组核心研究中发现的遗传变异的功能相关性，以及为临床和翻译核心的人类研究提供初步数据。动物模型核心有四个具体目标：(1)提供CKD、HTN和CVD小鼠模型的通道；(2)提供最先进的小鼠肾脏和心血管表型分析；(3)建立肾脏交叉移植模型，以区分肾脏和系统对小鼠生理、代谢和/或免疫功能的贡献；以及(4)对斑马鱼提供快速筛选对肾脏和/或心血管系统功能有影响的基因变体。

Chronic kidney disease (CKD) is associated with a marked increase in risk for cardiovascular disease (CVD), such that patients with CKD are more likely to die from CVD than to progress to end-stage renal disease. Hypertension (HTN) amplifies risk for CVD and affects more than 1 billion people worldwide. However, the causes of HTN cannot be determined in most patients and the mechanisms underlying the complex interactions among the kidney, HTN and cardiovascular disease and subsequent risk for mortality are not clear. We suggest that precise definition of these mechanisms will require multi-disciplinary teams with expertise in renal and cardiovascular systems. Accordingly, our objective is to provide a panel of sophisticated tools to support and facilitate multi-disciplinary, basic discovery research in animal models on the unique links relating the kidney, cardiovascular disease and HTN. The Core is configured to provide access to a range of experimental models of kidney, heart and vascular diseases, and Core personnel have comprehensive expertise in utilizing mouse models of CKD, CVD, and HTN, as well as functional kidney and cardiovascular screens in non-mammalian models. The Core will serve kidney or cardiovascular investigators who may be working in isolation to raise their awareness of the clinical impact of the heart-kidney axis and to provide access to models and techniques that can entice them to expand their efforts into our broader area of thematic interest. We will provide comprehensive phenotyping services for kidney, blood pressure and other cardiovascular functions. The scope of the Core will be Regional, National and International. Core staff will assist in experimental design as well as data collection and analysis. Capabilities of the Core will also be useful for determining functional relevance of genetic variants discovered in studies based in the Renal Genomics Core as well as providing preliminary data for human studies in the Clinical and Translational Core. The Animal Models Core has four specific aims: (1) to provide access to mouse models of CKD, HTN, and CVD; (2) to provide state-of-the-art kidney and cardiovascular phenotyping in mice; (3) to generate models of kidney cross-transplantation for distinguishing renal and systemic contributions to physiologic, metabolic and/or immunological functions in mice; and (4) to provide rapid screens in zebrafish for genetic variants with functional effects in kidney and/or cardiovascular system.