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

The vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) is the fir st endothelial receptor tyrosine kinase to be expressed in angioblast precu rsors, and its function is essential for the differentiation of endothelial cells and hematopoietic precursors. We have identified cis-acting regulato ry elements of the murine Flk-1 gene that mediate endothelium-specific expr ession 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 angio- bla sts and endothelial cells of transgenic mice, The intronic regulatory seque nces functioned as an autonomous endothelium-specific enhancer. Sequences o f the 5'-flanking region contributed to a strong, uniform, and reproducible transgene expression and were stimulated by the transcription factor HiF-2 alpha. The Flk-1 gene regulatory elements described in this study should a llow the elucidation of the molecular mechanisms involved in endothelial ce ll differentiation and angiogenesis. (C) 1999 by The American Society of He matology.