Mutations in the two major HCO3− exit pathways into the lumen, namely CFTR and DRA (Slc26a3), cause severe intestinal disease in humans [9, 15, 27], and the corresponding gene knockout is lethal for mice, pigs, and ferrets due to their intestinal phenotypes [20, 26, 32]. The gene discussed is SLC26A3; the disease is intestinal disorder.