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Endothelial-specific gene expression directed by the tie gene promoter in
vivo
J Korhonen, I Lahtinen, M Halmekyto, L Alhonen, J Janne, D Dumont and K Alitalo
Molecular/Cancer Biology Laboratory, Haartman Institute, University of
Helsinki, Finland.
The tie gene encodes a receptor tyrosine kinase that is expressed in the
endothelium of blood vessels, particularly during embryonic development and
angiogenesis in adults. We have cloned and characterized the mouse tie gene
and isolated the human and mouse tie promoters. The promoter activities of
human and mouse tie were analyzed using luciferase reporter gene constructs
in transfected cell lines and beta-galactosidase constructs in transgenic
mice. In transfection assays of cultured cells, both human and mouse
promoter DNA fragments showed activity that was not restricted to
endothelial cells. In contrast, in transgenic mice both promoters directed
expression of the reporter gene to endothelial cells undergoing
vasculogenesis and angiogenesis. In adult mice, tie promoter activity in
lung and many vessels of the kidney was as high as in the vessels of the
corresponding embryonic tissues, whereas in the heart, brain and liver, tie
promoter activity was downregulated and restricted to coronaries, cusps,
capillaries, and arteries. Our results show that the endothelial cell-type
specificity of the tie promoter in vivo can be transferred to heterologous
genes by using relatively short promoter fragments. The tie promoter, thus,
has useful properties for potential gene therapy.
Volume 86,
Issue 5,
pp. 1828-1835,
09/01/1995
Copyright © 1995 by The American Society of Hematology
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