Biomedical Research Core 2 - Rodent Models & Drug Testing Core

项目摘要-BRC 2 啮齿动物模型和药物测试核心的目标是联合收割机的发展创新的小鼠 模型和探索细胞特异性基因网络与基本药物测试服务，以推动PKD 社区在我们对多囊蛋白功能的理解，以及对治疗性 目标的将提供新的体内工具，以解决该领域的重大障碍，例如缺乏 遗传模型提供了对基因治疗潜在结果的深入了解，缺乏体内试剂， 可视化内源性多囊蛋白的亚细胞定位，以及缺乏表现出 人类疾病的常染色体显性遗传。利用KUMC在药物领域无与伦比的专业知识， 设计，药物测试和商业化，药物测试服务将提供，以满足需求， 需要进行实地的药物研究此外，通常使用的肾脏单核转录组图谱 将提供ADPKD的小鼠模型以帮助鉴定生物标志物和治疗靶点。 具体目标是：1）开发下一代小鼠模型以研究Pkd 1的遗传和功能 2）维持PKD啮齿动物模型和组织的活动物储存库以供分发; 3)在PKD啮齿动物模型中提供药物测试和饮食干预服务;以及4）提供纵向单一- 细胞核RNA-seq转录组学图谱来自快速和缓慢进展的Pkd 1突变小鼠。此外，核心 将提供咨询服务，并参加年度研讨会，以帮助研究人员了解 不同PKD模型赋予的各种效用，以更好地理解疾病过程， 临床前药物试验研究的设计。总的来说，这些服务将有利于研究任何 疾病的方面，并将改变多囊蛋白功能，疾病机制， 为国家PKD研究社区提供治疗。

Project Summary – BRC2 The goal of the Rodent Models & Drug Testing Core is to combine the development of innovative mouse models and exploration of cell-specific gene networks with essential drug-testing services to propel the PKD community forward in our understanding of polycystin function, and in identification and evaluation of therapeutic targets. Novel in vivo tools will be provided to address significant barriers in the field, such as the paucity of genetic models that provide insight into potential outcomes of gene therapy, the lack of in vivo reagents to visualize subcellular localization of endogenous polycystins, and the lack of a pre-clinical model that exhibits the autosomal dominant inheritance of the human disease. Using the unparalleled expertise of KUMC in drug design, drug testing and commercialization, a drug testing service will be offered to meet the demands of much needed drug studies in the field. Additionally, single nucleus transcriptomic maps of kidneys of commonly used mouse models of ADPKD will be provided to help with the identification of biomarkers and therapeutic targets. The specific aims are to: 1) develop next-generation mouse models to study the genetics and function of Pkd1 and other cystogenic genes; 2) maintain a live-animal repository of PKD rodent models and tissue for distribution; 3) provide drug testing and dietary intervention services in PKD rodent models; and 4) provide longitudinal single- nucleus RNA-seq transcriptomics maps from fast- and slow-progressing Pkd1-mutant mice. Further, the Core will provide consultation services and participate in an annual workshop to help researchers learn about the various utilities conferred by different PKD models for better understanding of disease processes and for the design of pre-clinical drug-testing studies. Collectively, these services will benefit investigators studying any aspect of the disease, and will transform investigations of polycystin function, disease mechanisms, and treatments for the national PKD research community.