Hepato-Renal Pathology in Pkd2WS25/- Mice, an Animal Model of Autosomal Dominant Polycystic Kidney Disease

Polycystic liver diseases, the most important of which are autosomal dominant and autosomal recessive polycystic kidney diseases, are incurable pathological conditions. Animal models that resemble human pathology in these diseases provide an opportunity to study the mechanisms of cystogenesis and to test potential treatments. Here we demonstrate that Pkd2(ws25/-) mice, an animal model of autosomal dominant polycystic kidney disease, developed hepatic cysts. As assessed by micro-computed tomography scanning of intact livers and by fight microscopy of hepatic tissue, hepatic cystic volumes increased from 12.82 +/- 3.16% (5- to 8-month-old mice) to 21.58 +/- 4.81% (9- to 12-month-old mice). Renal cystogenesis was more severe at early stages of disease: in 5- to 7-month-old mice, cystic volumes represented 40.67 +/- 5.48% of kidney parenchyma, whereas in older mice cysts occupied 31.04 +/- 1.88% of kidney parenchyma. Mild fibrosis occurred only in liver, and its degree was unchanged with age. Hepatic cysts were lined by single or multiple layers of squamous cholangiocytes. cystic cholangiocyte cilia were short and malformed, whereas in renal cysts they appeared normal. In Pkd(2ws25/-) mice, mitotic and apoptotic indices in both kidney and liver were increased compared with wild-type mice. In conclusion, Pkd2(ws25/-) mice exhibit hepatorenal pathology resembling human autosomal dominant polycystic kidney disease and represent a useful model to study mechanisms of cystogenesis and to evaluate treatment options. (Am J Pathol 2010, 176:1282-1291; DOI: 10.2353/ajpath.2010.090658)