THE PKD1 GENE PRODUCES A DEVELOPMENTALLY-REGULATED PROTEIN IN MESENCHYME AND VASCULATURE

Autosomal dominant polycystic kidney disease (ADPKD) is one of the mos t common human genetic diseases. In addition to polycystic kidneys, th e disease can cause cystic changes in liver and other organs, cardiac valvular insufficiency and cerebral arterial aneurysms. Using antibodi es raised against the predicted gene product of PKD1, which is mutated in about 85% of ADPKD cases, we show that PKD1 is a 530-kD protein lo calized to the extracellular matrix of kidney, liver and cerebral bloo d vessels. We discovered that the PKD1 protein was highly expressed in the mesenchyme of developing kidney and liver, transiently localized in the developing glomerulus and juxtaglomerular apparatus and restric ted to perivascular, extraglomerular areas in adult renal cortex. Thes e data suggest that the PKD1 protein plays a role in renal and hepatic morphogenesis.