Abstract
The interferon-regulated mouse Mx gene encodes the 72-kilodalton nuclear Mx protein that selectively inhibits influenza virus replication. Mice carrying Mx+ alleles synthesize Mx protein and resist influenza virus infection, whereas mice homozygous for Mx- alleles fail to synthesize Mx protein and, as a consequence, are influenza virus susceptible. Southern blot analysis allowed us to define the following three distinct Mx restriction fragment length polymorphism (RFLP) types among classical inbred strains: RFLP type 1 in the Mx+ strains A2G and SL/NiA, RFLP type 2 in BALB/c and 33 other Mx- strains, and RFLP type 3 in CBA/J and 2 other Mx- strains. cDNA clones of Mx mRNAs from BALB/c and CBA/J cells were isolated, and their sequences were compared with that of the wild-type Mx mRNA of strain A2G. Mx mRNA of BALB/c mice has 424 nucleotides absent from the coding region, resulting in a frame shift and premature termination of Mx protein. The missing sequences correspond exactly to Mx exons 9 through 11. These three exons, together with some flanking intron sequences, are deleted from the genomes of all Mx RFLP type 2 strains. The Mx- phenotype of the Mx RFLP type 3 strain CBA/J is due to a point mutation that converts the lysine codon in position 389 to a termination codon. Mx RFLP type 3 strains have an extra HindIII site which maps to an intron and thus probably does not affect the coding capacity of Mx mRNA. We further show that the Mx mRNA levels in interferon-treated BALB/c and CBA/J cells are about 15-fold lower than in similarly treated Mx+ cells. This is probably due to decreased metabolic stabilities of the mutant mRNAs.
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- Arnheiter H., Staeheli P. Expression of interferon dependent resistance to influenza virus in mouse embryo cells. Arch Virol. 1983;76(2):127–137. doi: 10.1007/BF01311696. [DOI] [PubMed] [Google Scholar]
- Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
- Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins F. S., Weissman S. M. The molecular genetics of human hemoglobin. Prog Nucleic Acid Res Mol Biol. 1984;31:315–462. doi: 10.1016/s0079-6603(08)60382-7. [DOI] [PubMed] [Google Scholar]
- Dreiding P., Staeheli P., Haller O. Interferon-induced protein Mx accumulates in nuclei of mouse cells expressing resistance to influenza viruses. Virology. 1985 Jan 15;140(1):192–196. doi: 10.1016/0042-6822(85)90460-x. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Ferris S. D., Sage R. D., Wilson A. C. Evidence from mtDNA sequences that common laboratory strains of inbred mice are descended from a single female. Nature. 1982 Jan 14;295(5845):163–165. doi: 10.1038/295163a0. [DOI] [PubMed] [Google Scholar]
- Haller O., Acklin M., Staeheli P. Influenza virus resistance of wild mice: wild-type and mutant Mx alleles occur at comparable frequencies. J Interferon Res. 1987 Oct;7(5):647–656. doi: 10.1089/jir.1987.7.647. [DOI] [PubMed] [Google Scholar]
- Haller O. Inborn resistance of ice to orthomyxoviruses. Curr Top Microbiol Immunol. 1981;92:25–52. doi: 10.1007/978-3-642-68069-4_3. [DOI] [PubMed] [Google Scholar]
- Horisberger M. A., Staeheli P., Haller O. Interferon induces a unique protein in mouse cells bearing a gene for resistance to influenza virus. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1910–1914. doi: 10.1073/pnas.80.7.1910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hug H., Costas M., Staeheli P., Aebi M., Weissmann C. Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter. Mol Cell Biol. 1988 Aug;8(8):3065–3079. doi: 10.1128/mcb.8.8.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milner R. J., Sutcliffe J. G. Gene expression in rat brain. Nucleic Acids Res. 1983 Aug 25;11(16):5497–5520. doi: 10.1093/nar/11.16.5497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nave K. A., Lai C., Bloom F. E., Milner R. J. Jimpy mutant mouse: a 74-base deletion in the mRNA for myelin proteolipid protein and evidence for a primary defect in RNA splicing. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9264–9268. doi: 10.1073/pnas.83.23.9264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noteborn M., Arnheiter H., Richter-Mann L., Browning H., Weissmann C. Transport of the murine Mx protein into the nucleus is dependent on a basic carboxy-terminal sequence. J Interferon Res. 1987 Oct;7(5):657–669. doi: 10.1089/jir.1987.7.657. [DOI] [PubMed] [Google Scholar]
- Okayama H., Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170. doi: 10.1128/mcb.2.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Staeheli P., Danielson P., Haller O., Sutcliffe J. G. Transcriptional activation of the mouse Mx gene by type I interferon. Mol Cell Biol. 1986 Dec;6(12):4770–4774. doi: 10.1128/mcb.6.12.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staeheli P., Dreiding P., Haller O., Lindenmann J. Polyclonal and monoclonal antibodies to the interferon-inducible protein Mx of influenza virus-resistant mice. J Biol Chem. 1985 Feb 10;260(3):1821–1825. [PubMed] [Google Scholar]
- Staeheli P., Haller O., Boll W., Lindenmann J., Weissmann C. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Cell. 1986 Jan 17;44(1):147–158. doi: 10.1016/0092-8674(86)90493-9. [DOI] [PubMed] [Google Scholar]
- Staeheli P., Haller O. Interferon-induced Mx protein: a mediator of cellular resistance to influenza virus. Interferon. 1987;8:1–23. [PubMed] [Google Scholar]
- Staeheli P., Horisberger M. A., Haller O. Mx-dependent resistance to influenza viruses is induced by mouse interferons alpha and beta but not gamma. Virology. 1984 Jan 30;132(2):456–461. doi: 10.1016/0042-6822(84)90050-3. [DOI] [PubMed] [Google Scholar]
- Staeheli P., Pravtcheva D., Lundin L. G., Acklin M., Ruddle F., Lindenmann J., Haller O. Interferon-regulated influenza virus resistance gene Mx is localized on mouse chromosome 16. J Virol. 1986 Jun;58(3):967–969. doi: 10.1128/jvi.58.3.967-969.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staeheli P., Sutcliffe J. G. Identification of a second interferon-regulated murine Mx gene. Mol Cell Biol. 1988 Oct;8(10):4524–4528. doi: 10.1128/mcb.8.10.4524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeshita K., Forget B. G., Scarpa A., Benz E. J., Jr Intranuclear defect in beta-globin mRNA accumulation due to a premature translation termination codon. Blood. 1984 Jul;64(1):13–22. [PubMed] [Google Scholar]