Generation and Analysis of Serine Protease Inhibitor Kazal Type 3-Cre Driver Mice

Serine protease inhibitor Kazal type 1 (<i>SPINK1</i>; mouse homologue <i>Spink3</i>) was initially discovered as a trypsin-specific inhibitor in the pancreas. However, previous studies have suggested that <i>SPINK1/Spink3</i> is expressed in a wide range of normal tissues and tumors, although precise characterization of its gene expression has not been described in adulthood. To further analyze <i>Spink3</i> expression, we generated two mouse lines in which either <i>lacZ</i> or Cre recombinase genes were inserted into the <i>Spink3</i> locus by Cre-<i>loxP</i> technology. In <i>Spink3^lacZ</i> mice, β-galactosidase activity was found in acinar cells of the pancreas and kidney, as well as epithelial cells of the bronchus in the lung, but not in the gastrointestinal tract or liver. <i>Spink3^cre</i> knock-in mice were crossed with Rosa26 reporter (R26R) mice to monitor Spink3 promoter activity. In <i>Spink3^cre</i>;R26R mice, β-galactosidase activity was found in acinar cells of the pancreas, kidney, lung, and a small proportion of cells in the gastrointestinal tract and liver. These data suggest that Spink3 is widely expressed in endoderm-derived tissues, and that <i>Spink3^cre</i> knock-in mice are a useful tool for establishment of a conditional knockout mice to analyze Spink3 function not only in normal tissues, but also in tumors that express <i>SPINK1/Spink3</i>.