Recapitulating polycystic kidney disease in mice

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is primarily characterized by the formation of thousands of kidney cysts, is caused by mutations in the PKD1 or PKD2 gene, and affects 0.1% of the population. However, also cyst formation in liver and pancreas can occur and there is a higher chance of developing aneurisms. No safe and effective therapy exists to treat ADPKD patients. In this thesis we generated a conditional Pkd1 knock-out mouse model in which we specifically can follow the disease progression in the kidney in more detail. This led to a further characterization of the mechanism behind cyst formation. In addition we report two different therapeutic strategies that effectively inhibited cyst formation in mice. The results in this thesis therefore have led to an improved understanding of cyst formation and to an improved understanding in how to inhibit this process, which ultimately might contribute to finding a clinically relevant therapy for patients.