Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase

Double-stranded RNA-dependent protein kinase (PKR) has been implicated in interferon (IFN) induction, antiviral response and tumor suppression, We have generated mice devoid of functional PKR (Pkr(o/o)), Although the mice are physically normal and the induction of type I IFN genes by poly(I). poly(C) (pIC) and virus is unimpaired, the antiviral response induced by IFN-gamma and pIC was diminished, However, in embryo fibroblasts from Pkr knockout mice, the induction of type I IFN as well as the activation of NF-kappa B by pIC, were strongly impaired but restored by priming with IFN. Thus, PKR is not directly essential for responses to pIC, and a pIC-responsive system independent of PKR is induced by IFN, No evidence of the tumor suppressor activity of PKR was demonstrated.