[en] Allelic polymorphisms at the mouse Mx1 locus affect the probability of survival after experimental influenzal disease, raising the possibility that marker-assisted selection using the homologous locus could improve the innate resistance of pigs to natural influenza infections. Several issues need to be resolved before efficient large scale screening of the allelic polymorphism at the porcine (Sus scrofa) Mx1 locus can be implemented. First, the Mx1 genomic structure has to be established and sufficient flanking intronic sequences have to be gathered to enable simple PCR amplification of the coding portions of the gene. Then, a basic knowledge of the promoter region needs to be obtained as an allelic variation there can significantly alter absolute levels and/or tissue-specificity of MX protein expression. The results gathered here show that the porcine Mx1 gene and promoter share the major structural and functional characteristics displayed by their homologs described in cattle, mouse, chicken, and man. The crucial function of the proximal interferon-sensitive response elements motif for gene expression is also demonstrated. The sequence data compiled here will allow an extensive analysis of the polymorphisms present among the widest spectrum possible of porcine breeds with the aim to identify an Mx1 allele providing antiviral resistance.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Thomas, Anne; Université de Liège - ULiège > Morphologie et Pathologie > Pathologie spéciale
Palm, Mélanie; Université de Liège - ULiège > Morphologie et Pathologie > Pathologie spéciale et autopsies
Broers, Aurore ; Université de Liège - ULiège > Morphologie et Pathologie > Pathologie spéciale et autopsies
Zezafoun, Hussein ; Université de Liège - ULiège > Morphologie et Pathologie > Pathologie spéciale et autopsies
Desmecht, Daniel ; Université de Liège - ULiège > Morphologie et Pathologie > Pathologie spéciale et autopsies
Language :
English
Title :
Genomic structure, promoter analysis, and expression of the porcine (Sus scrofa) Mx1 gene
Publication date :
2006
Journal title :
Immunogenetics
ISSN :
0093-7711
eISSN :
1432-1211
Publisher :
Springer Verlag, New York, United States - New York
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403-410
Arnheiter H, Skuntz S, Noteborn M, Chang S, Meier E (1990) Transgenic mice with intracellular immunity to influenza virus. Cell 62:51-61
Asano A, Jin HK, Watanabe T (2003) Mouse Mx2 gene: organization, mRNA expression and the role of the interferon-response promoter in its regulation. Gene 306:105-113
Baise E, Pire G, Leroy M, Gerardin J, Goris N, De Clercq K, Kerkhofs P, Desmecht D (2004) Conditional expression of type I interferon-induced bovine MX1 GTPase in a stable transgenic vero cell line interferes with replication of vesicular stomatitis virus. J Interferon Cytokine Res 24:513-521
Chang KC, Hansen E, Foroni L, Lida J, Goldspink G (1991) Molecular and functional analysis of the virus- and interferon-inducible human MxA promoter. Arch Virol 117:1-15
Collet B, Secombes CJ (2001) The rainbow trout (Oncorhynchus mykiss) Mx1 promoter. Structural and functional characterization. Eur J Biochem 268:1577-1584
Frese M, Kochs G, Feldmann H, Hertkorn C, Haller O (1996) Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MXA protein. J Virol 70:915-923
Gérardin JA, Baise EA, Pire GA, Leroy MP, Desmecht DJ (2004) Genomic structure, organisation, and promoter analysis of the bovine (Bos taurus) Mx1 gene. Gene 326:67-75
Gongora C, Degols G, Espert L, Hua TD, Mechti N (2000) A unique ISRE, in the TATA-less human Isg20 promoter, confers IRF-1-mediated responsiveness to both interferon type I and type II. Nucleic Acids Res 28:2333-2341
Haller O, Frese M, Kochs G (1998) MX proteins: mediators of innate resistance to RNA viruses. Rev Sci Tech Off Int Épizoot 17:220-230
Hu CH, Harris JE, Davie EW, Chung DW (1995) Characterization of the 5′-flanking region of the gene for the alpha chain of human fibrinogen. J Biol Chem 270:28342-28349
Hug H, Costas M, Staeheli P, Aebi M, Weissmann C (1988) Organisation of the murine Mx gene and characterization of its interferon- and virus-inducible promoter. Mol Cell Biol 8:3065-3079
Lee S-H, Vidal SM (2002) Functional diversity of the MX proteins: variations on a theme of host resistance to infection. Genome Res 12:527-530
Lindenmann J (1962) Resistance of mice to mouse-adapted influenza a virus. Virology 16:203
Melen K, Ronni T, Broni B, Krug RM, von Bonsdorff CH, Julkunen I (1992) Interferon-induced MX proteins form oligomers and contain a putative leucine zipper. J Biol Chem 267:25898-25907
Muller M, Winnacker EL, Brem G (1992) Molecular cloning of porcine Mx cDNAs: new members of a family of interferon-inducible proteins with homology to GTP-binding proteins. J Interf Res 12:119-129
Nicholas B, Karl B, Nicholas P, Hugh JrB (1997) GeneDoc: a tool for editing and annotating multiple sequence alignments. http://www.psc.edu/biomed/ genedoc
Pahl HL, Baeuerle PA (1995) Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B. J Virol 69:1480-1484
Pavlovic J, Zurcher T, Haller O, Staeheli P (1990) Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MXA protein. J Virol 64:3370-3375
Reid LE, Brasnett AH, Gilbert CS, Porter AC, Gewert DR, Stark GR, Kerr IM (1989) A single DNA response element can confer inducibility by both alpha- and gamma-interferons. Proc Natl Acad Sci USA 86:840-844
Ronni T, Matikainen S, Lehtonen A, Palvimo J, Dellis J, Van Eylen F, Goetschy JF, Horisberger M, Content J, Julkunen I (1998) The proximal interferon-stimulated response elements are essential for interferon responsiveness: a promoter analysis of the antiviral MxA gene. J Interferon Cytokine Res 18:773-781
Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365-386
Shapiro MB, Senapathy P (1987) RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res 15:7155-7174
Tazi-Ahnini R, di Giovine FS, McDonagh AJ, Messenger AG, Amadou C, Cox A, Duff GW, Cork MJ (2000) Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region. Hum Genet 106:639-645
Van der Bliek AM (1999) Functional diversity in the dynamin family. Trends Cell Biol 9:96-102
Zhang DE, Hetherington CJ, Tan S, Dziennis SE, Gonzalez DA, Chen HM, Tenen DG (1994) Sp1 is a critical factor for the monocytic specific expression of human CD14. J Biol Chem 269:11425-11434
Zhang Z, Fuentes NL, Fuller GM (1995) Characterization of the IL-6 responsive elements in the gamma fibrinogen gene promoter. J Biol Chem 270:24287-24291