In vivo expression of murine platelet glycoprotein Ibα
In vivo expression of murine platelet glycoprotein Ibα
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DOI：
10.1182/blood.v92.2.488.414k03_488_495
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发表时间：
1998-07-15
期刊：
影响因子：
20.3
通讯作者：
Ware, J
中科院分区：
文献类型：
--
作者：
Fujita, H;Hashimoto, Y;Ware, J
我们已经进行了系统的基因表达的小鼠血小板粘附受体，GP Ib-IX-V的糖蛋白（GP）Ib α亚基的体内评价。这项研究是必要的人GP Ib α表达的非造血谱系细胞的体外观察和报告的GP Ib α基因的细胞因子的调节。然而，GP Ib-IX-V受体的体内作用尚未确定，超出了对正常巨核细胞/血小板生理学和止血的描述。我们对小鼠器官的北方分析显示，骨髓中GP Ib α mRNA水平较高，在含有受鼠GP Ib α启动子控制的荧光素酶转基因的小鼠中重现了类似的表达模式。在小鼠的两个造血器官，骨髓（1，400相对光单位/μ g蛋白[RLU]）和脾脏（500 RLU）中观察到一致的高水平荧光素酶活性，在心脏、主动脉和肺（30至60 RLU）中观察到可再现但低水平的荧光素酶活性。在循环血细胞中，荧光素酶活性仅定位于血小板中。用脂多糖（LPS）或肿瘤坏死因子-α（TNF-α）处理小鼠后，未观察到GP Ib α mRNA或荧光素酶活性增加。我们得出结论，鼠GP Ib α启动子支持巨核细胞中高水平的基因表达，并且可以表达异源蛋白，从而允许在血小板的独特环境中体内操纵血小板特异性蛋白，（C）1998，美国血液学学会。
We have performed a systematic in vivo evaluation of gene expression for the glycoprotein (GP) Ib alpha subunit of the murine platelet adhesion receptor, GP Ib-IX-V. This study is warranted by in vitro observations of human GP Ib alpha expression in cells of nonhematopoietic lineage and reports of regulation of the GP Ib alpha gene by cytokines. However, an in vivo role for a GP Ib-IX-V receptor has not been established beyond that described for normal megakaryocyte/platelet physiology and hemostasis. Our Northern analysis of mouse organs showed high levels of GP Ib alpha mRNA in bone marrow with a similar expression pattern recapitulated in mice containing a luciferase transgene under the control of the murine GP Ib alpha promoter. Consistently high levels of luciferase activity were observed in the two hematopoietic organs of mice, bone marrow (1,400 relative light units/mu g of protein [RLUs]) and spleen (500 RLUs), Reproducible, but low-levels of luciferase activity were observed in heart, aorta, and lung (30 to 60 RLUs). Among circulating blood cells, the luciferase activity was exclusively localized in platelets. No increase in GP Ib alpha mRNA or luciferase activity was observed after treatment of mice with lipopolysaccharides (LPS) or tumor necrosis factor-alpha (TNF-alpha). We conclude the murine GP Ib alpha promoter supports a high level of gene expression in megakaryocytes and can express heterologous proteins allowing an in vivo manipulation of platelet specific proteins in the unique environment of a blood platelet, (C) 1998 by The American Society of Hematology.