SMAD4 and colitis: To determine the effect of epithelial-specific loss of Smad4 on colitis response in an acute DSS mouse model, we first knocked out Smad4 in the epithelium (Smad4IEC−KO) using the Villin promoter–driven, tamoxifen-inducible, Cre-recombinase (17) (Fig S1B) and assessed the colitis response to 2.5% DSS (40 kD) in drinking water for 7 d.