Mx1 causes resistance against influenza A viruses in the Mus spretus-derived inbred mouse strain SPRET/Ei
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Updated: Jul 6, 2026
Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
Ineke Vanlaere1, Ananza Vanderrijst, Jean-Louis Guénet
1Department for Molecular Biomedical Research, VIB, Technologiepark 927, B-9052 Ghent, Belgium.
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.
Insights
SPRET/Ei mice exhibit strong resistance to influenza A virus infection due to a functional Mx1 gene. Congenic mice show that variations in Mx1 alleles impact protection levels, highlighting Mx1
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- Inbred SPRET/Ei mice, derived from Mus spretus, show extreme resistance to influenza A virus.
- This resistance is linked to the interferon-inducible Mx1 gene on distal chromosome 16, which encodes a protein stimulating innate immunity against Orthomyxoviruses.
- While most inbred mouse strains have a defective Mx1 gene, SPRET/Ei possesses a functional allele.
Purpose of the Study:
- To investigate the functional significance of sequence variations between Mx1 alleles from Mus spretus and Mus musculus (A2G strain).
- To compare the protective effects of different Mx1 alleles in a controlled genetic background.
Main Methods:
- Utilized congenic mouse strains with Mx1 genes from M. spretus or A2G in a C57BL/6 background.
- Infected congenic mice with a highly pathogenic influenza virus strain.
- Analyzed Mx1 gene induction levels using RT-PCR and Western blot.
Main Results:
- Congenic mice carrying the M. spretus Mx1 gene (B6.spretus-Mx1) demonstrated superior protection against influenza infection compared to those with the A2G Mx1 gene (B6.A2G-Mx1).
- Differences in Mx1 induction levels may explain the observed variations in protection.
- RT-PCR and Western blot confirmed differential Mx1 induction.
Conclusions:
- SPRET/Ei mice represent a novel resource for studying Mx1 biology due to their functional Mx1 allele.
- Sequence variations in Mx1 alleles can significantly influence innate immunity and protection against influenza virus.
- The study establishes a basis for further research into Mx1-mediated antiviral mechanisms.
