Biomedical Research Core 2 - Rodent Models & Drug Testing Core

项目总结- BRC2

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.