Generation of Ifit2/ISG54 and Ifit1/ISG56 knockout mice Ifit2 gene knockout (Ifit2 2/2 ) mice were generated by deleting the entire protein-encoding region of the gene, which was achieved by flanking exons 2 and 3 with frt recombinase sites in C57BL/6 embryonic stem cells and excising the flanked region with Flp recombinase ( Figure 1A ). Ifit2 2/2 mice were bred to homozygosity ( Figure 1B) , and deficiency for induced expression of Ifit2 protein was confirmed in lysates of IFN-b-treated primary murine embryonic fibroblasts (MEF) ( Figure 1C ). Mice deficient for Ifit1 (Ifit1 2/2 ) were derived from C57BL/6 embryonic stem cells lacking the entire Ifit1 coding region ( Figure 1A ). Genotypic homozygosity of the Ifit1 2/2 mice and deficiency for Ifit1 protein induction were confirmed ( Figure 1B and 1C ). Both knockout mouse lines were healthy and fertile. Moreover, deletion of one gene within the Ifit locus did not alter the pattern of induction of other adjacent gene family members, as compared to wild-type (wt) mice ( Figure 1C ).