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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4284-4292
Identification of Vascular Endothelial Growth Factor (VEGF) Receptor-2
(Flk-1) Promoter/Enhancer Sequences Sufficient for Angioblast
and Endothelial Cell-Specific Transcription in Transgenic Mice
Andreas Kappel,
Volker Rönicke,
Annette Damert,
Ingo Flamme,
Werner Risau, and
Georg Breier
From the Max-Planck-Institute for Physiological and Clinical
Research, Bad Nauheim, Germany; the Zentrum für molekulare
Medizin, Köln, Germany.
The vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) is
the first endothelial receptor tyrosine kinase to be expressed in
angioblast precursors, and its function is essential for the differentiation of endothelial cells and hematopoietic precursors. We
have identified cis-acting regulatory elements of the murine Flk-1 gene that mediate endothelium-specific expression of a
LacZ reporter gene in transgenic mice. Sequences within the
5'-flanking region of the Flk-1 gene, in combination with
sequences located in the first intron, specifically targeted transgene
expression to angioblasts and endothelial cells of transgenic mice. The
intronic regulatory sequences functioned as an autonomous
endothelium-specific enhancer. Sequences of the 5'-flanking
region contributed to a strong, uniform, and reproducible transgene
expression and were stimulated by the transcription factor HIF-2 .
The Flk-1 gene regulatory elements described in this study
should allow the elucidation of the molecular mechanisms involved in
endothelial cell differentiation and angiogenesis.
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