GENDER-DEPENDENT DISEASE SEVERITY IN AUTOSOMAL POLYCYSTIC KIDNEY-DISEASE OF RATS

The impact of gender on the course of chronic renal failure in polycys tic kidney disease (PKD) has been under discussion for years. Recently an animal model of autosomal dominant PKD in the rat became available allowing this topic to be studied. The aim of this study was to evalu ate disease severity according to gender, and the occurrence of antici pation and/or genetic imprinting. Male and female affected PKD rats we re crossed with respective Wistar-Ottawa-Karlsburg (WOK) rats. From th is P generation 26 affected F1 hybrids were obtained, which were then backcrossed with WOK rats, resulting in 275 backcrosses (BC generation ). In BC rats the affected males had a significantly higher kidney wei ght, worse histology and poorer renal function than the females. In th e male, but not the female rats of the BC generation, transmission fro m an affected F1 mother resulted in significantly higher kidney weight , worse histology and poorer renal function than when the gene was inh erited through an affected father. Since at the same time body and kid ney weight were higher in the respective unaffected males, the previou s effect in the affected rats might be due to a growth factor transfer red by the mother's milk. The sex of the P generation had no such impa ct on these parameters. Thus our data provide no evidence for disease anticipation and genetic imprinting (in the classical sense) in the PK D rats, and the assumption of a gender-dependent disease expressivity is favored.