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转基因小鼠中人类C反应蛋白基因的调控

Regulation of the human C-reactive protein gene in transgenic mice.

作者信息

Murphy C, Beckers J, Rüther U

机构信息

European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.

出版信息

J Biol Chem. 1995 Jan 13;270(2):704-8. doi: 10.1074/jbc.270.2.704.

Abstract

Human C-reactive protein (hCRP) is a major acute-phase reactant in man. The regulation of the hCRP gene in transgenic mice is similar to that in humans. To map DNA regions required for the correct regulation of the hCRP gene, several constructs have been generated, and their expression in transgenic mice has been analyzed. Constructs lacking DNA regions surrounding the poly(A) site of the gene are not expressed either before or after induction in transgenic mice. Minimal regions 540 base pairs upstream and 1.2 kilobases downstream of the hCRP gene are sufficient for liver-specific expression. Extended 5'- and 3'-flanking regions are required to silence the expression prior to induction. Our findings demonstrate that regulatory sequences shown to confer inducible expression of the hCRP gene in hepatoma cell lines are insufficient in transgenic mice.

摘要

人C反应蛋白(hCRP)是人类主要的急性期反应物。hCRP基因在转基因小鼠中的调控与人相似。为了绘制hCRP基因正确调控所需的DNA区域,已构建了几种构建体,并分析了它们在转基因小鼠中的表达。缺乏该基因聚腺苷酸化位点周围DNA区域的构建体在转基因小鼠诱导前后均不表达。hCRP基因上游540个碱基对和下游1.2千碱基的最小区域足以实现肝脏特异性表达。需要延伸的5'和3'侧翼区域在诱导前使表达沉默。我们的研究结果表明,在肝癌细胞系中显示可赋予hCRP基因诱导表达的调控序列在转基因小鼠中是不足的。

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