The Vascular Endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice
The Vascular Endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice
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DOI：
10.1182/blood.v93.1.184.401a20_184_192
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发表时间：
1999-01-01
期刊：
影响因子：
20.3
通讯作者：
Huber, P
中科院分区：
文献类型：
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作者：
Gory, S;Vernet, M;Huber, P
血管内皮钙粘蛋白（Vascular endothelial-cadherin，VE-cadherin）是一种钙依赖性粘附分子，在内皮细胞中特异性表达。在牛主动脉内皮细胞中，VE-钙粘蛋白启动子与报告基因融合的分析显示了三个主要的功能区域，（-139，+24）促进非特异性转录;的加入（-289，-140）和（-2226，-1190）结构域消除了成纤维细胞中的转录，而内皮细胞中的表达保持不变，这表明片段（-2226，+24）和更长的片段包含完整的内源启动子活性。为了研究启动子区域在体内的转录特异性，我们产生了携带含有（-2486，+24）区域的嵌合构建体的转基因小鼠。该启动子指导报告基因在成年转基因小鼠的所有检查器官中表达。在胚胎发育过程中，在血管发生的早期阶段检测到转基因表达。后来，在血管系统发育过程中表达持续存在，并仅限于血管的内皮层。总之，这些数据为VE-钙粘蛋白启动子内的特定调控区域提供了证据。此外，鉴定限制基因表达至内皮的DNA序列对于开发心血管或血管生成疾病的动物模型或用于递送治疗分子具有许多潜在的应用。(C)1999年，美国血液学会。
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. (C) 1999 by The American Society of Hematology.