title: Mx1 causes resistance against influenza A viruses in the Mus spretus-derived inbred mouse strain SPRET/Ei.
abstract: Inbred SPRET/Ei mice, derived from Mus spretus, were found to be extremely resistant to infection with a mouse adapted influenza A virus. The resistance was strongly linked to distal chromosome 16, where the interferon-inducible Mx1 gene is located. This gene encodes for the Mx1 protein which stimulates innate immunity to Orthomyxoviruses. The Mx1 gene is defective in most inbred mouse strains, but PCR revealed that SPRET/Ei carries a functional allele. The Mx1 proteins of M. spretus and A2G, the other major resistant strain derived from Mus musculus, share 95.7% identity. We were interested whether the sequence variations between the two Mx1 alleles have functional significance. To address this, we used congenic mouse strains containing the Mx1 gene from M. spretus or A2G in a C57BL/6 background. Using a highly pathogenic influenza virus strain, we found that the B6.spretus-Mx1 congenic mice were better protected against infection than the B6.A2G-Mx1 mice. This effect may be due to different Mx1 induction levels, as was shown by RT-PCR and Western blot. We conclude that SPRET/Ei is a novel Mx1-positive inbred strain useful to study the biology of Mx1.
authors.affiliation: Department for Molecular Biomedical Research, VIB, Technologiepark 927, B-9052 Ghent, Belgium.
authors.forename: Ineke
authors.initials: I
authors.lastname: Vanlaere
authors.forename: Ananza
authors.initials: A
authors.lastname: Vanderrijst
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guénet
authors.forename: Marina
authors.initials: M
authors.lastname: De Filette
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
mesh_terms: D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008040:Genetic Linkage; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000821:virology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins; D009976:Orthomyxoviridae Infections / Q000378:metabolism*; D016415:Sequence Alignment; D015996:Survival Rate
chemical_list: C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins