title: Mouse Mx2 gene: organization, mRNA expression and the role of the interferon-response promoter in its regulation.
abstract: 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.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. atasano@vetmed.hokudai.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Asano
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D016475:3T3 Cells; D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005796:Genes / Q000235:genetics; D007372:Interferons / Q000494:pharmacology*; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009115:Muridae; D009154:Mutation; D064547:Myxovirus Resistance Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
chemical_list: C579070:Mx1 protein, mouse; C579067:Mx2 protein, mouse; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D003609:Dactinomycin; D004247:DNA; D007372:Interferons; D003513:Cycloheximide; D008156:Luciferases; D019204:GTP-Binding Proteins