The pck rat: A new model that resembles human autosomal dominant polycystic kidney and liver disease

Background. The pck rat is a recently identified model of polycystic kidney disease (PKD) and liver disease (PLD) that developed spontaneously in the rat strain Crj:CD/SD. Its pattern of inheritance is autosomal recessive. Methods. To characterize this new model, we studied pck rats derived from F 9 breeding pairs from Charles River Japan and control Sprague-Dawley rats. Blood and tissues (kidneys, liver, and pancreas), obtained from these rats at 1, 7, 21, 70, and 182 days of age, were used for biochemical determinati ons, light and electron microscopy, and immunohistochemistry. Results. The pck rats develop progressive cystic enlargement of the kidneys after the first week of age, and liver cysts are evident by day 1. The ren al cysts developed as a focal process from thick ascending loops of Henle, distal tubules, and collecting ducts in the corticomedullary region and out er medulla. Flat and polypoid epithelial hyperplasia were common in dilated tubules and cysts. Apoptosis was common and affected normal, as well as di lated tubules, but less frequently cysts lined by flat epithelium. The base ment membranes of the cyst walls exhibited a variety of alterations, includ ing thinning, lamellation, and thickening. Focal interstitial fibrosis and inflammation were evident by 70 days of age. Segmental glomerulosclerosis a nd segmental thickening of the basement membrane with associated effacement of the podocyte foot processes were noted in some rats at 70 days of age. The PKD was more severe in male than in female pck rats, as reflected by th e higher kidney weights, while there was no gender difference in the severi ty of the PLD. Mild bile duct dilation was present as early as one day of a ge. With age, it became more severe, and the livers became markedly enlarge d. Even then, however, there was only a mild increase in portal fibrosis, w ithout formation of fibrous septae. Slight elevations of plasma blood urea nitrogen levels were detected at 70 and 182 days of age. Conclusions. The pck rat is a new inherited model of PKD and PLD with a nat ural history and renal and hepatic histologic abnormalities that resemble h uman autosomal dominant PKD. This model may be useful for studying the path ogenesis and evaluating the potential therapies for PKD and PLD. The identi fication of the pck gene may provide further insight into the pathogenesis of autosomal dominant PKD.