Bono P, Salmi M, Smith D J, Leppänen I, Horelli-Kuitunen N, Palotie A, Jalkanen S
MediCity Research Laboratories, University of Turku, National Public Health Institute, Finland.
J Immunol. 1998 Sep 15;161(6):2953-60.
Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule which mediates lymphocyte binding to endothelial cells. The cloning of a mouse VAP-1 (mVAP-1) cDNA revealed that mVAP-1 is a novel 110/220 kDa transmembrane molecule with significant identity to copper-containing amine oxidases. In this work the nucleotide sequence and primary structure of the mVAP-1 gene was determined and the promoter region was structurally characterized. The isolated approximately 14.4-kb mVAP-1 gene consists of 4 exons and 3 introns. Primer extension analysis and 5' rapid amplification of cDNA ends revealed multiple transcription initiation sites in different tissues suggesting that the mVAP-1 transcription is differently regulated in different tissues. Analysis of the sequence immediately upstream of the detected transcription initiation sites showed no canonical TATA or CCAAT elements, but putative regulatory elements were found close to the detected transcription start sites. The cloning of the mVAP-1 gene reveals the first insight into the genomic organization of murine amine oxidases and will, by targeted disruption of the gene, allow us to understand better the importance of VAP-1 in leukocyte trafficking and monoamine oxidase activity for the function of the immune system.
血管黏附蛋白-1（VAP-1）是一种内皮细胞黏附分子，可介导淋巴细胞与内皮细胞的结合。小鼠VAP-1（mVAP-1）cDNA的克隆显示，mVAP-1是一种新型的110/220 kDa跨膜分子，与含铜胺氧化酶具有显著同源性。在这项研究中，确定了mVAP-1基因的核苷酸序列和一级结构，并对启动子区域进行了结构表征。分离得到的约14.4 kb的mVAP-1基因由4个外显子和3个内含子组成。引物延伸分析和cDNA末端的5'快速扩增揭示了不同组织中的多个转录起始位点，这表明mVAP-1转录在不同组织中受到不同调控。对检测到的转录起始位点上游紧邻序列的分析未发现典型的TATA或CCAAT元件，但在检测到的转录起始位点附近发现了推定的调控元件。mVAP-1基因的克隆首次揭示了小鼠胺氧化酶的基因组组织情况，通过对该基因的靶向破坏，将使我们能够更好地理解VAP-1在白细胞运输和单胺氧化酶活性对免疫系统功能中的重要性。
