INDUCIBLE AND TISSUE-SPECIFIC EXPRESSION OF HUMAN C-REACTIVE PROTEIN IN TRANSGENIC MICE

INDUCIBLE AND TISSUE-SPECIFIC EXPRESSION OF HUMAN C-REACTIVE PROTEIN IN TRANSGENIC MICE
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DOI:
10.1002/j.1460-2075.1987.tb02745.x
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发表时间:
1987-12-01
期刊:
影响因子:
11.4
通讯作者:
RUTHER, U
RUTHER, U
中科院分区:
生物学1区
文献类型:
--
作者:
CILIBERTO, G;ARCONE, R;RUTHER, U

文献摘要

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c反应蛋白(CRP)是人体内主要的急性期反应物,而不是小鼠体内的。人肝细胞在多种疾病(主要是急性炎症)过程中大量合成。为了研究CRP的表达调控,通过微量注射将人CRP基因引入受精卵,并获得转基因小鼠系。CRP基因仅在肝脏中转录,其表达严格依赖于实验性炎症。诱导RNA和蛋白质合成的动力学非常快;RNA在肝脏中2小时后可首次检测到,蛋白在血清中6小时后可首次检测到。转基因小鼠血清中的人类CRP水平与在人类疾病中观察到的水平相当。核运行实验表明,调控主要是在转录水平。
C-reactive protein (CRP) is a major acute phase reactant in man but not in mouse. It is synthesized in abundant quantities by human hepatocytes during the course of several diseases, mainly acute inflammations. To investigate the regulation of CRP expression, the human CRP gene was introduced into fertilized eggs by microinjection and transgenic mouse lines were derived. The CRP gene is exclusively transcribed in the liver and expression is strictly dependent on experimental inflammation. The kinetics of induction both for RNA and protein synthesis is very fast; RNA is first dectable after 2 h in the liver, the protein after 6 h in the serum. Human CRP levels in the sera of transgenic mice are comparable to those observed in human diseases. Nuclear runon experiments indicate that regulation is primarily at the transcriptional level.