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

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human genetic diseases. In addition to polycystic kidneys, the disease can cause cystic changes in liver and other organs, cardiac valvular insufficiency and cerebral arterial aneurysms. Using antibodies 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 localized to the extracellular matrix of kidney, liver and cerebral blood 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 restricted to perivascular, extraglomerular areas in adult renal cortex. These data suggest that the PKD1 protein plays a role in renal and hepatic morphogenesis.