Carbonic anhydrase II gene expression in mouse pancreatic duct cells

Our goal is to create a transgenic mouse model for human pancreatic duct cell adenocarcinoma using the promoter/enhancer region of the carbonic anhydrase (CA) II gene to drive the expression of SV-40 T-antigen in pancreatic duct cells. This requires that the CA II gene be expressed in mouse pancreatic duct cells and not in other pancreatic cells, as has already been shown to be the case in the human and guinea pig pancreas. We have shown with an enzyme histochemical assay that mouse pancreatic duct cells contain CA activity in both intact pancreas and cultured interlobular duct epithelium. In addition, CA activity was detected with a biochemical assay in homogenates of cultured duct epithelium. The specific activity of duct cells was 2.75-fold greater than in whole pancreas, suggesting that a substantial amount of total pancreatic CA activity is contributed by duct cells. At least some of the CA in cultured duct cells was inferred to be CA II by Northern blot analysis of RNA extracted from the cells. The concentration of CA II mRNA in the cultured duct cells was substantially greater than in whole pancreas and would appear to account for the majority, if not all, of the CA II in the mouse pancreas.