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

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  • S. Gory
    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.
  • M. Vernet
    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.
  • M. Laurent
    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.
  • E. Dejana
    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.
  • J. Dalmon
    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.
  • 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.

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<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

Journal

  • Blood

    Blood 93 (1), 184-192, 1999-01-01

    American Society of Hematology

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