MICE DEVOID OF INTERFERON REGULATORY FACTOR-1 (IRF-1) SHOW NORMAL EXPRESSION OF TYPE-I INTERFERON GENES

The transcription factor interferon regulatory factor 1 (IRF-1) binds tightly to the interferon (IFN)-beta promoter and has been implicated in the induction of type I IFNs. We generated mice devoid of functiona l IRF-1 by targeted gene disruption. As reported by others, IRF-1-defi cient mice showed a discrete phenotype: the CD4/CD8 ratio was increase d and IFN-gamma-induced levels of macrophage iNO synthase mRNA were st rongly diminished. However, type I IFN induction in vivo by virus or d ouble-stranded RNA was unimpaired, as evidenced by serum IFN titers an d IFN mRNA levels in spleen, liver and lung. There was also no impairm ent in the response of type I IFN-inducible genes. Therefore, IRF-1 is not essential for these processes irt vivo.