These and other spontaneous models (Tg737orpk/orpk and Bicc1bpk/bpk mice and Pkhd1PCK/PCK rats) have helped identify disease genes, have been invaluable for studying disease mechanisms, and have been used extensively for preclinical trials.81, , , , , –87 Although the main focus of this review is on ADPKD orthologous disease models, many insights and applications in ADPKD have been obtained through study of these nonorthologous spontaneous models (including disease mechanisms and preclinical studies), highlighting overlap in PKD mechanisms and the value of these models. Here, BTK is linked to autosomal dominant polycystic kidney disease.