The Vascular Endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice

Vascular endothelial-cadherin (VE-cadherin) is a calcium-dependent adhesive molecule, exclusively and constitutively expressed in endothelial cells. A nalysis of the VE-cadherin promoter fused to a reporter gene in bovine aort ic endothelial cells showed three major functional regions, The proximal re gion alone (-139, +24) promoted nonspecific transcription; the addition of the (-289, -140) and (-2226, -1190) domains abolished transcription in fibr oblasts while expression in endothelial cells remained unchanged, suggestin g that fragments (-2226, +24) and longer contain the full endogenous promot er activity. To study the transcriptional specificity of the promoter regio n in vivo, we generated transgenic mice carrying the chimeric construct con taining the (-2486, +24) region. The promoter directed reporter expression in all examined organs of adult transgenic mice. During embryonic developme nt, transgene expression was detected at the early steps of vasculogenesis. Later, the expression persisted during development of the vascular system and was restricted to the endothelial layer of the vessels. Together, these data provide evidence for specific regulatory regions within the VE-cadher in promoter. Furthermore, the identification of DNA sequences restricting g ene expression to the endothelium has many potential applications for the d evelopment of animal models of cardiovascular or angiogenic diseases or for the delivery of therapeutic molecules. (C) 1999 by The American Society of Hematology.