Mx1 causes resistance against influenza A viruses in the Mus spretus-derived inbred mouse strain SPRET/Ei

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 stimul...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 2008-04, Vol.42 (1), p.62-70
Main Authors: Vanlaere, Ineke, Vanderrijst, Ananza, Guénet, Jean-Louis, De Filette, Marina, Libert, Claude
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Body Weight
Congenic mice
Female
Genetic Linkage
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Humans
Immunity, Innate
Influenza
Influenza A virus
Influenza A virus - metabolism
Lung - cytology
Lung - virology
Male
Mice
Mice, Congenic
Molecular Sequence Data
Mus musculus
Mus spretus
Mx1
Myxovirus Resistance Proteins
Orthomyxoviridae Infections - metabolism
Resistance
Sequence Alignment
Survival Rate
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Summary: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.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2008.01.013