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 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-2alpha. 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.
Kappel
A
A
Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany; the Zentrum für molekulare Medizin, Köln, Germany.
Rönicke
V
V
Damert
A
A
Flamme
I
I
Risau
W
W
Breier
G
G
D016475:3T3 Cells; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002417:Cattle; D004730:Endothelium, Vascular / Q000196:embryology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor; D012045:Regulatory Sequences, Nucleic Acid; D013234:Stem Cells / Q000378:metabolism*; D014158:Transcription, Genetic; D015017:Yolk Sac / Q000098:blood supply; D001616:beta-Galactosidase / Q000235:genetics
D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D001616:beta-Galactosidase