In addition to these physiological similarities, the DNR line serves as an effective model of human IBD because (i) human IBD is associated with mutations in SMAD3 (5, 60, –, 62), a direct downstream target of TGF-β RII required for Foxp3 induction in the gut (33), and (ii) DNR mice model the documented effect of Smad7 overexpression in human IBD (63, –, 65). This evidence concerns the gene SMAD3 and inflammatory bowel disease.