Tissue-specific transcriptional activity of a pancreatic islet cell-specific enhancer sequence/Pax6-binding site determined in normal adult tissues in vivo using transgenic mice

A pancreatic islet cell-specific enhancer sequence (PISCES) shared by the r at insulin-I, glucagon, and somatostatin genes binds the paired domain-cont aining transcription factor Pax6 and confers strong transcriptional activit y in pancreatic islet cell lines. It was found recently that Pax6 plays a m ajor role in islet development. In the present study, transgenic mice were used to investigate PISCES-mediated transcription in normal adult islets in vivo. In several independent mouse lines expressing a PISCES-luciferase re porter transgene, the PISCES motif directed gene expression in the adult ey e, cerebellum, and discrete brain areas, consistent with the tissue distrib ution of Pax6. These tissues contain two Pax6 isoforms caused by alternativ e splicing, only one of which was found to bind the PISCES motif in electro phoretic mobility shift assays. No reporter gene expression was detected in adult pancreatic islets or in any other peripheral organ tested. RT-PCR an alysis confirmed that Pax6 mRNA is present in adult islets. These results d emonstrate that the PISCES motif is sufficient to direct highly tissue-spec ific gene expression in whole animals. The lack of PISCES-mediated transcri ption in adult islets indicates that the Pax6 protein(s) expressed in adult pancreatic islets function differently from the ones in the eye and cerebe llum.