In the ring with polycystic kidney disease—avoiding the knockout punch

AbstractAutosomal dominant polycystic kidney disease (PKD) is an inherited disease that results from mutations in either polycystin (PKD1) or polycystin 2 (PKD2), both of which are large, complex, and multifunctional proteins whose loss results in the development of numerous fluid‐filled cysts and fibrosis that compromise renal function. A number of spontaneous and engineered mouse models of PKD have provided some understanding of many aspects of cyst development, modifier genes, and mechanistic pathways, but fall short of reproducing the human disease accurately. Two recent papers in The Journal of Pathology set out new models using miRNA, or inducible and targeted recombination, that achieve partial or timed suppression of Pkd1. Instead of knocking out Pkd1 immediately, or completely, these more subtle approaches may help deliver more faithful models of this significant human renal disease. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Invited Commentary for Hassane S, Leonhard WN, van der Wal A, et al. Elevated TGFβ–Smad signalling in experimental Pkd1 models and human patients with polycystic kidney disease. J Pathol 2010; 222: 21–31. And for Wang E, Hsieh‐Li HM, Chiou YY, et al. Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against Pkd1. J Pathol 2010; 222: 238–248.