SMAD4 and colonic neoplasm: Therefore, to directly demonstrate the contribution of IFN-γ in the pathogenesis of inflammation-driven colon cancer in Smad4TKO mice, we introduced the lineage-restricted SMAD4 deletion (Smad4TKO) onto a genetic background with a germ line IFN-γ deletion (IFN-γKO) to generate a ‘double knockout’ (Smad4TKO/IFN-γKO, DKO) model.