Von Willebrand factor promoter targets the expression of amyloid beta protein precursor to brain vascular endothelial cells of transgenic mice.
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 beta protein precursor protein (AbetaPP) isoforms 695 and 751 (wild-type and Dutch variant mutations) under the regulation of this VWF promoter sequence. These AbetaPP 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.
Jahroudi
Nadia
N
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. njahroud@aecom.yu.edu
Schmaier
Alvin
A
Srikanth
Sujata
S
Mahdi
Fakhri
F
Lutka
Frances A
FA
Bowser
Robert
R
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D014841:von Willebrand Factor / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor; D014841:von Willebrand Factor