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The mouse Mx1 gene encodes an interferon (IFN)-inducible nuclear protein and confers resistance to influenza virus infection. The standard laboratory mouse strains all carry the Mx1− allele and are susceptible to influenza virus. In this study, several mouse strains established from wild mice were tested to determine their Mx1+ or Mx1− allele status with polymerase chain reaction-restriction fragment length variation (PCR-RFLV), sequence analysis, reverse transcription (RT)-dimmunofluorescence staining. All of the mouse strains originating from wild mice were found uniformly to carry the Mx1+ allele. Therefore, it is conceivable that the Mx1+ allele in wild populations serves a function against some pathogens related to orthomyxoviruses. The PCR-RFLV and sequence analysis allowed us to classify the Mx1+ alleles of the laboratory and wild-origin mouse strains into distinct classes. RT-PCR and immunofluorescence staining demonstrated that the Mx1 transcripts and proteins were induced by IFN-α/β in macrophages from wild mouse species.