Mouse Mx2 gene:: organization, mRNA expression and the role of the interferon-response promoter in its regulation

Mouse Mx2 gene:: organization, mRNA expression and the role of the interferon-response promoter in its regulation
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DOI:
10.1016/s0378-1119(03)00428-1
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发表时间:
2003-03-13
期刊:
影响因子:
3.5
通讯作者:
Watanabe, T
Watanabe, T
中科院分区:
生物学3区
文献类型:
--
作者:
Asano, A;Jin, HK;Watanabe, T

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Mx是在多种脊椎动物中发现的干扰素(IFN)诱导的细胞内蛋白,其介导对负链RNA病毒的抗性。我们先前已经证明,野生小鼠品系能够表达功能性Mx 2 mRNA,而近交系实验室品系的Mx 2 mRNA由于开放阅读框中的单核苷酸插入而无功能,并且在可检测水平下。在本研究中,我们研究了Mx2的表达在体内的调节使用同源小鼠携带Mx 1和Mx2基因来自野生型菌株SPR。IFN α/β处理后,Mx2 mRNA在脾脏、卵巢和白色脂肪组织中被强烈诱导。此外,我们还鉴定了Mx2基因的结构。它由14个外显子组成,与Mx 1基因高度同源。Mx2的启动子区含有两个假定的IFN刺激反应元件(ISRE)。我们发现,位于-69和-55之间的近端ISRE位点对于使用具有Mx2启动子突变体的报告基因构建体的瞬时转染测定的IFN α/β诱导的转录是必需的。这些结果表明Mx基因之间的mRNA诱导机制的相似性。(C)2003 Elsevier Science B. V.保留所有权利。
Mx is an interferon (IFN)-inducible intracellular protein found in various vertebrates that mediates resistance against negative-strand RNA viruses. We have demonstrated previously that feral mouse strains are able to express a functional Mx2 mRNA, while that of the inbred laboratory strains was non-functional because of a single nucleotide insertion in the open reading frame, and under the detectable level. In the present study, we examined the regulation of Mx2 expression in vivo using a congenic mouse carrying Mx1 and Mx2 genes derived from feral strain SPR. Mx2 mRNA was induced strongly in the spleen, ovary and white adipose tissue after the treatment with IFNalpha/beta. Furthermore, we identified the structure of the Mx2 gene. It consists of 14 exons, greatly homologous to the Mx1 gene. The promoter region of Mx2 contained two putative IFN-stimulated response elements (ISREs). We found that the proximal ISRE site positioned between -69 and -55 was essential to IFNalpha/beta-induced transcription by transient transfection assay using reporter gene constructs with mutants of the Mx2 promoter. These results indicate the similarity of the mechanisms of mRNA induction among Mx genes. (C) 2003 Elsevier Science B.V. All rights reserved.