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

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.