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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 184-192
The Vascular Endothelial-Cadherin Promoter Directs
Endothelial-Specific Expression in Transgenic Mice
S. Gory,
M. Vernet,
M. Laurent,
E. Dejana,
J. Dalmon, and
P. Huber
From the Commissariat à l'Energie Atomique (CEA),
Laboratoire de Transgenèse et Différenciation Cellulaire,
Département de Biologie Moléculaire et Structurale,
Grenoble, France; and the Istituto di Ricerche Farmacologiche Mario
Negri, Milan, Italy.
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-cadherin
promoter. 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.
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