The Vascular Endothelial-Cadherin Promoter Directs Endothelial-Specific Expression in Transgenic Mice

Abstract

Vascular endothelial-cadherin (VE-cadherin) is a calcium-dependent adhesive molecule, exclusively and constitutively expressed in endothelial cells. Analysis of the VE-cadherin promoter fused to a reporter gene in bovine aortic endothelial cells showed three major functional regions. The proximal region alone (−139, +24) promoted nonspecific transcription; the addition of the (−289, −140) and (−2226, −1190) domains abolished transcription in fibroblasts while expression in endothelial cells remained unchanged, suggesting that fragments (−2226, +24) and longer contain the full endogenous promoter activity. To study the transcriptional specificity of the promoter region in vivo, we generated transgenic mice carrying the chimeric construct containing the (−2486, +24) region. The promoter directed reporter expression in all examined organs of adult transgenic mice. During embryonic development, 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-cadherinpromoter. Furthermore, the identification of DNA sequences restricting gene expression to the endothelium has many potential applications for the development of animal models of cardiovascular or angiogenic diseases or for the delivery of therapeutic molecules.

Divergent roles of endothelial NF-κB in multiple organ injury and bacterial clearance in mouse models of sepsis

“…Using an extended Tie promoter coupled to the Tet-on system, Teng et al were able to drive LacZ expression on the endothelium of adult mice, although those mice have leakiness ( 39 ). In the current study, we took a different approach by using the VE -cadherin-5 promoter ( 21 ) to drive endothelial-selective rtTA expression and by generating multiple independent rtTA and TreI-B ␣ mt mouse lines. Intercrossing between those independent rtTA and TreI-B ␣ mt lines produced 42 double TG mouse lines, which allowed us to select the best dual TG lines.…”

“…We achieved endothelium-restricted rtTA expression using the vascular endothelial (VE) -cadherin-5 promoter, which has been shown to drive endothelial-specifi c transgene expression in widespread organs in TG mice ( 21 ). I-B ␣ mt expression was controlled by a TreCMV fusion promoter, whose activation requires the binding of rtTA and Dox ( Fig.…”

Breaking the VE‐cadherin bonds

“…In endothelial cells, VE-cadherin is highly expressed and located at adherens junctions. Its expression profile appears early and is restricted to the endothelial cell lineage, such that its promoter has been used to generate transgene expression specifically in the endothelial compartment [7]. In addition, N-cadherin is also found at high levels in endothelial cells but exhibits a weak clustering at the endothelial cell-cell junctions and occupied preferentially apical locations.…”

The milk thistle (Silybum marianum) compound Silibinin stimulates leukopoiesis from mouse embryonic stem cells

“…In additional experiments, we investigated whether L‐NAME (100 μM) would inhibit VEGFR2 and VE‐cadherin expression (Figure e,f). VE‐cadherin is an endothelium‐specific protein required for proper vasculogenesis (Gory et al, ). Indeed, the data of the present study clearly demonstrate that inhibition of STAT3 and PI3K/AKT abolished VEGFR2 and HIF‐1α expression upon Silibinin (10 μM) treatment.…”