Translational research in ADPKD: lessons from animal models

Mice with mutations in Pkd1 or Pkd2 enable a step-by-step analysis of the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and valuable insights into early and progressive disease stagesMouse models have shown that mutations in genes encoding polycystin proteins cause renal cysts, but additional factors are also required for cyst formationRenal injury accelerates the rate of cyst formation, probably by increasing the chance that cysts are formedAnimal studies have revealed a complex network of genetic and functional interactions between different renal cystic disease genes involved in polycystic kidney diseaseDifferences in lifespan, metabolism, renal anatomy, involved nephron segment and genetic background mean that a mouse model cannot perfectly recapitulate human ADPKDThe question of which mouse models of ADPKD are the most suitable to study disease mechanisms and for preclinical testing does not have a definitive answer