Biomedical Research Core 2 - Rodent Models & Drug Testing Core

生物医学研究核心 2 - 啮齿动物模型

• 批准号: 10475045
• 负责人: Pamela Vivian Tran
• 金额: $ 19.03万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10475045
• 关键词: Biomedical Research; Kansas; Research; Rodent Model; Translations; drug testing

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.

项目摘要-BRC2 啮齿动物模型和药物检测核心的目标是结合创新小鼠的开发 以基本药物测试服务推动PKD的细胞特异性基因网络的模型和探索 社区在我们对多囊藻毒素功能的理解以及在识别和评估治疗方面的进展 目标。将提供新的活体工具来解决该领域的重大障碍，例如缺乏 提供对基因治疗潜在结果的洞察的遗传模型，体内试剂的缺乏 可视化内源性多囊蛋白的亚细胞定位，以及缺乏临床前模型显示 人类疾病的常染色体显性遗传。利用KUMC无与伦比的专业知识在药物领域 设计、药物测试和商业化，将提供药物测试服务，以满足许多需求 需要实地进行药物研究。此外，常用的肾脏单核转录图谱 将提供ADPKD的小鼠模型，以帮助识别生物标记物和治疗靶点。 本研究的具体目的是：1)建立新一代小鼠模型，研究PKD1的遗传学和功能 和其他致囊基因；2)维护用于分布的PKD啮齿动物模型和组织的活体动物储存库； 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)提供纵向单一干预服务 来自快速和缓慢进展的PKD1突变小鼠的核RNA-seq转录图谱。更进一步，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 不同的PKD模型赋予的各种实用程序，以更好地了解疾病过程和 临床前药物试验研究的设计。总的来说，这些服务将使研究任何 在疾病方面，并将改变对多囊藻毒素功能、疾病机制和 为国家PKD研究界提供的治疗。