ABSTRACT
Vascular complications including intracranial aneurysms are a major cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD). Almost all cases of ADPKD are caused by mutations in either PKD1 or PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively, which are expressed in all types of endothelial cells. Pkd1 and Pkd2 knockout mice die during mid-gestation with a dramatic vascular phenotype that includes focal hemorrhage, edema, defective vascularization of the fetal placenta and polyhydramnios. Selective inactivation of Pkd1 or Pkd2 in endothelial cells results in a subset of the “vascular” phenotypes previously identified in null animals. At the cellular level, endothelial cells lacking expression of polycystins are defective in their response to fluid shear stress while Pkd1/2 mutant lymphatic endothelial cells fail to migrate properly. Together the data indicate a functional role for polycystins in the vasculature. In this chapter, we review the tools that can be applied to study the role of polycystins in endothelial cells. These include mouse models and assays that use tissues from Pkd1/2 mutant mice. In addition, we describe methods for generating Pkd1/2 mutant endothelial cells, which can be used in a variety of assays to evaluate the effects of polycystin depletion.
