Core C: Murine Models and Biobank

项目总结 多囊肾病(PKD)是由PKD1、PKD2和PKHD1基因突变引起的遗传性疾病。PKD IS 是终末期肾病的重要原因，通常需要肾移植或透析。从基因上讲 工程化小鼠模型在揭示PKD发病机制的关键特征方面发挥了重要作用。准确 预测PKD的小鼠模型结合疾病机制的新兴知识现在已经 推介这些有价值的模型以推动在发现和验证新产品方面取得前所未有的进步 靶向治疗和新的早期诊断/疾病进展生物标志物。实现这一目标的重要障碍 这些令人兴奋的可能性是调查人员在选择、获取和适当使用 PKD鼠标模型资源。在过去的P30支持期间，我们一直在积极提供 研究人员用PKD小鼠品系和组织病理学支持，导致了一些高 影响研究。对于此次更新，核心C、鼠标模型和Biobank核心的总体目标是 继续促进使用PKD鼠标模型的翻译研究项目。我们的具体目标是：1) 为PKD社区提供活体小鼠生物资源，包括广泛使用的PKD模型和模型 具有复杂的基因类型；2)开发并提供4个关键的小鼠模型，这将是特别的 对于研究人员培育小鼠模型和进行自己的临床前试验很有用3)以提供 小鼠模型和病理专业知识以及组织满足局部(包括核心B和核心D)和 国家PKD研究基地需要；4)为开发的候选疗法提供定制的临床前测试 由研究人员在适当的PKD小鼠模型上进行测试；以及5)为PKD研究基地提供 获得用于创建和冷冻保存PKD新小鼠模型的全方位转基因服务 研究。总之，为反映PKD相关功能而设计的小鼠模型提供了一个强大的工具 发现治疗PKD的新治疗方法。

PROJECT SUMMARY Polycystic kidney disease (PKD) is genetic disorder caused by mutations in PKD1, PKD2 and PKHD1. PKD is an important cause of end stage renal disease and often requires renal transplantation or dialysis. Genetically engineered mouse models have been instrumental in unraveling key features of PKD pathogenesis. Accurate and predictive mouse models of PKD coupled with emerging knowledge of disease mechanisms has now positioned these valuable models to drive unprecedented advancement in the discovery and validation of new targeted therapies and new early diagnosis/disease progression biomarkers. An important obstacle in realizing these exciting possibilities is a need by investigators for support in choosing, acquiring, and appropriately using PKD mouse model resources. Over the past period of P30 support we have been active in supplying investigators with PKD mouse lines and the histopathologic support that has resulted in a number of high impact studies. For this renewal, the overall goal of Core C, the Mouse Models and Biobank Core, is to continue to facilitate translational research projects using PKD mouse models. Our specific aims are: 1) to provide a live mouse bioresource for the PKD community consisting of widely used PKD models and models with complex genotypes; 2) to develop and make available 4 key mouse models that would be particularly useful for investigators for breeding mouse models and performing their own preclinical trials 3) to provide mouse model and pathology expertise as well as tissues to meet the local (including Core B and Core D) and national PKD research base needs; 4) to provide custom preclinical testing of candidate therapies developed by investigators for testing in appropriate PKD mouse models; and 5) to provide the PKD research base with access to a full range of transgenic services for creating and cryopreserving new mouse models for PKD research. In summary, Mouse models engineered to mirror relevant features of PKD provide a powerful tool for discovering new therapeutic approaches to treating PKD.