Polycystic kidney disease (PCKD) is responsible for 5-10% of end stage renal disease in the United States. The pathogenesis of cyst formation is poorly understood. Cyst development has been studied in a variety of chemically induced models in laboratory animals and in polycystic kidneys from humans obtained at nephrectomy or autopsy. Spontaneously occurring PCKD has been described in lambs, piglets, cats, dogs, rats, antelope and mice. Of these, only the mouse has been maintained as a spontaneous genetic model of Infantile Polycystic Kidney Disease (IPCD). A major limitation of the mouse model, particularly for investigation of biochemical alterations associated with cyst development, is the small size of developing feti and neonates. In addition, there are morphologic differences between the cystic condition in mice and IPCD. This application is directed towards the development and maintenance of recently identified naturally occurring polycystic kidney disease model in newborn piglets. The mode of inheritance of this trait will be determined. We will describe the morphologic features of this disease with urographic studies, microdissection, light and electron microscopic examination. We will study cyst development in fetuses and neonates with microdissection and organ enzyme analysis including Na+ K+ - ATPase and Mg++ - ATPase evaluation. We will analyze cyst fluid and serum biochemically. We will study the growth characteristics of cyst epithelium in cell culture. A long term goal is to make affected piglets or carrier breeding animals available to qualified investigators.
