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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3405-3412
Characterization of the Mouse von Willebrand Factor Promoter
Jiazhen Guan,
Pascale V. Guillot, and
William C. Aird
From the Department of Medicine, Divisions of Molecular Medicine and
Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA.
Expression of the von Willebrand factor (vWF) gene is restricted to
the endothelial and megakaryocyte lineages. Within the endothelium,
expression of vWF varies between different vascular beds. We have
previously shown that the human vWF promoter spanning a region between
 2182 (relative to the start site of transcription) and the end of
the first intron contains information for environmentally responsive,
vascular bed-specific expression in the heart, skeletal muscle, and
brain. In the present study, we cloned the mouse vWF (mvWF) promoter
and studied its function in cultured endothelial cells and transgenic
mice. In transient transfection assays, the mvWF gene was found to be
regulated by distinct mechanisms in different endothelial cell
subtypes. In independent lines of transgenic mice, an mvWF promoter
fragment containing DNA sequences between 2645 and the end of the
first intron directed endothelial cell-specific expression in the
microvascular beds of the heart, brain, and skeletal muscle as well as
the endothelial lining of the aorta. In 1 line of mice, reporter gene
activity was also detected in bone marrow megakaryocytes. Taken
together, these findings suggest that both the mouse and human vWF
promoters are regulated by vascular bed-specific mechanisms.
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