EPIDERMAL GROWTH-FACTOR RECEPTOR ACTIVITY MEDIATES RENAL CYST FORMATION IN POLYCYSTIC KIDNEY-DISEASE

A consistent phenotype observed in both human patients and several dif ferent mouse models of autosomal recessive polycystic kidney disease ( ARPKD) is an increased activity of the epidermal growth factor recepto r (EGFR) in the affected kidneys. To determine whether this increased activity of the EGFR is a functional event that is directly part of th e disease pathway of renal cyst formation, we used a genetic approach to introduce a mutant EGFR with decreased tyrosine kinase activity int o a murine model of ARPKD, We found that the modified form of the EGFR could block the increase in EGFR-specific tyrosine kinase activity th at normally accompanies the development of renal cysts, and this corre lated with an improvement in kidney function and a substantial decreas e in cyst formation in the collecting ducts, These results suggest tha t changes in the expression of the EGFR contribute to the formation of cysts in the collecting ducts, and that drugs that target the tyrosin e kinase activity of the EGFR may potentially be therapeutic in ARPKD.