Mice heterozygous for Sptbn1, encoding the multifunctional Smad3 adaptor protein βII-spectrin (β2SP), alone or when combined with the heterozygosity of Smad3 (Sptbn1+/−, Smad3+/−Sptbn1+/−) spontaneously develop GI cancers and hepatocellular cancer (HCC) in the C57BL/6J background [13, 21]. The gene discussed is SMAD3; the disease is hepatocellular carcinoma.