EXPRESSION OF HUMAN ALPHA-1-ACID GLYCOPROTEIN GENES IN CULTURED-CELLS AND IN TRANSGENIC MICE
EXPRESSION OF HUMAN ALPHA-1-ACID GLYCOPROTEIN GENES IN CULTURED-CELLS AND IN TRANSGENIC MICE
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DOI：
10.1101/gad.2.2.259
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发表时间：
1988-02-01
影响因子：
10.5
通讯作者：
CORTESE, R
中科院分区：
文献类型：
--
作者：
DENTE, L;RUTHER, U;CORTESE, R
人类基因组包含三个α1-糖蛋白基因(AGP-A、AGP-B和AGP-B‘’)，编码的蛋白质形式略有不同。在血浆中发现的人α1-酸性糖蛋白的主要成分由AGP-A编码，AGP-A在肝脏和肝癌细胞系中表达，由炎症刺激诱导。我们通过将克隆的AGP-A基因导入肝脏和非肝脏来源的细胞系，研究了其对AGP-A基因的调节作用。与到目前为止研究的任何其他肝脏特异性基因不同，每一种测试的AGP构建体在肝癌和HeLa细胞中都以同样的效率表达。相比之下，转基因小鼠中相同的结构以组织特异性的方式表达，并受到急性时相刺激的调节。携带三个AGP基因簇的转基因小鼠分泌血清中的人类蛋白，相应的mRNA主要来自AGP-A基因。这种mRNA是肝脏特异的，在实验诱导的炎症后，它的浓度增加了几倍。其他仅携带AGP-A基因的转基因株系显示，6.6kb的片段包含足够的组织特异性和受调控表达的信息，该片段包括整个编码区以及1.2kb的5‘’侧翼和2-kb的3‘侧翼DNA。
The human genome contains three .alpha.1-glycoprotein genes (AGP-A, AGP-B, and AGP-B'') encoding for slightly different forms of the protein. The major component of human .alpha.1-acid glycoprotein found in plasma is coded by AGP-A, which is expressed in liver and in hepatoma cell lines and is induced by inflammatory stimuli. We have studied the regulation of the cloned AGP-A gene by transfection into cell lines of hepatic and nonhepatic origin. Unlike any other liver-specific gene investigated so far, every AGP construct tested was expressed with comparable efficiency in hepatoma and HeLa cells. In contrast, identical constructs in transgenic mice are expressed in a tissue-specific manner and are regulated by acute-phase stimuli. Transgenic mice carrying the cluster of three AGP genes secrete the human protein in the serum, and the corresponding mRNA is mainly derived from the AGP-A gene. The mRNA is liver specific, and its concentration increases several fold following experimentally induced inflammation. Additional transgenic lines carrying only the AGP-A gene showed that sufficient information for tissue-specific and regulated expression is contained within a 6.6-kb segment comprising the whole coding region plus 1.2-kb 5''-flanking and 2-kb 3''-flanking DNA.