Figure 1: Cyst initiation in ADPKD requires a secondary insult.
Although ADPKD is dominantly inherited, cyst initiation is recessive at the cellular level. Cyst initiation occurs when tubule epithelial cells harboring one mutated allele of Pkd1 or Pkd2 receive a secondary insult, either by spontaneous somatic mutation of the healthy allele (two-hit hypothesis) or by any mechanism that reduces the function of the polycystin proteins below a critical threshold (threshold model). Created with BioRender.com
