Of the TGF-β-signaling-deficient colon cancer mouse models, the immunocompetent Smad3 knockout (Smad3−/−) mouse is the model of choice (23) because the Tgfb1−/−Rag2−/− model is immunodeficient (20), the TGFβR2-deficient mouse is embryonic lethal (24), and the intestine-specific Tgfbr2 knockout mouse must be combined with another colon tumor suppressor (8). Here, SMAD3 is linked to colonic neoplasm.