Experimental approach to test the hypothesis of ductal cells as pancreatic progenitors. (A) Our hypothesis is that with replication, mature duct cells regress to a less differentiated phenotype and then act as pancreatic progenitors to form new acini, islets, and ducts. (B) Tg mice in which human CAII promoter drives Cre or CreERTM expression were generated (CAII-Cre and CAII-CreERTM) and crossed with a Cre-mediated recombination reporter strain, R26R. In the double-Tg mice (CAII-Cre; R26R), if CAII-expressing ductal cells serve as pancreatic progenitors after birth, we should find β-galactosidase-positive cells not only in ducts but also in islets and acini; however, if duct cells do not act as progenitors, only ducts should be labeled.