Development of a Porcine Model of Autosomal Dominant Polycystic Kidney Disease

DESCRIPTION (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, potentially fatal genetic disorders in humans with an incidence of 1 in every 500-1000 individuals. The majority of ADPKD cases (85%) are caused by mutations in the PKD1 gene, which encodes polycystin-1. ADPKD is a systemic disorder that often leads to kidney failure and extrarenal manifestations including the development of cysts in the liver and pancreas, hypertension, intracranial aneurysms, cardiac valve abnormalities, aortic dissection, and abdominal wall hernias. Despite significant progress in our understanding of this disease, there are no approved treatments to reverse or slow the progression of ADPKD. Much of what is known about ADPKD has come from studying Pkd1 mutant mice. While the orthologous murine models have been very useful for understanding some aspects of the disease, they do not recapitulate human disease progression or its dominant inheritance, and they fail to develo