Von Willebrand factor promoter targets the expression of amyloid β protein precursor to brain vascular endothelial cells of transgenic mice

Abstract

Dysfunction of brain vascular endothelial cells may be associated with the pathogenesis of several diseases including cerebral amyloid angiopathy, hemorrhagic stroke and Alzheimer disease. New model systems are necessary to examine the contribution of brain endothelial cells in these disorders. The Von Willebrand factor gene promoter fragment that spans sequences -487 to +247 targets the expression of LacZ marker gene in transgenic mice specifically to brain vascular endothelial cells. Transgenic mice have been prepared that express human amyloid β protein precursor protein (AβPP) isoforms 695 and 751 (wild-type and Dutch variant mutations) under the regulation of this VWF promoter sequence. These AβPP transgenes are specifically expressed in brain vascular endothelial cells. The VWF promoter is a valuable tool for targeting gene expression to brain vascular endothelial cells to provide a model to directly examine endothelial cell placement of genes and their contribution to cerebral vascular disease.