Rodent Autosomal Dominant Polycystic Kidney Disease Models

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic nephropathy. Nonetheless, limited therapeutic options are available to patients. The development of successful interventions relies heavily on understanding the pathomechanisms driving cyst initiation and expansion. As a result, researchers have turned to rodent models for providing mechanistic insight. In the subsequent chapter, we provide a detailed discussion of the generation, phenotype analyses, principal findings, and preclinical use of PKD rodent models. We also outline the foundation laid by these models for our current understanding of PKD pathomechanisms. Principally, regardless of genetic insult, transgenic, inducible/conditional knockout, and knock-in murine ADPKD models faithfully develop gross manifestations of clinical ADPKD such as increased kidney weight–to–body weight ratio, renal cysts, and fibrosis, as well as decreased kidney function. Importantly, murine ADPKD models have allowed for the elucidation of ADPKD protein function, revealed a complex network of genetic interactions driving cystogenesis, exposed the disrupted cellular signaling networks associated with or supportive of cyst progression, identified the role of primary cilia in PKD, and provided a translational platform for testing the therapeutic efficacy of numerous potential interventions.