Pax-2 activates the proglucagon gene promoter but is not essential for proglucagon gene expression or development of proglucagon-producing cell lineages in the murine pancreas or intestine.
Tissue-specific proglucagon gene transcription is achieved through combinations of transcription factors expressed in pancreatic A cells and enteroendocrine L cells of the small and large intestine. Cell transfection and electrophoretic mobility shift assay experiments previously identified Pax-2 as a regulator of islet proglucagon gene expression. We examined whether Pax-2 regulates gut proglucagon gene expression using enteroendocrine cell lines and Pax2(1NEU) mutant mice. Immunoreactive Pax-2 was detected in STC-1 enteroendocrine cells, and Pax-2 activated proglucagon promoter activity in transfected baby hamster kidney and GLUTag cells. Pax-2 antisera diminished the formation of a Pax-2-G3 complex in electrophoretic mobility shift assay studies using nuclear extracts from islet and enteroendocrine cell lines. Surprisingly, Pax-2 mRNA transcripts were not detected by RT-PCR in RNA isolated from adult rat pancreas, rat islets, embryonic d 19 or adult murine pancreas and gastrointestinal tract. Furthermore, embryonic d 19 or neonatal d 1 Pax2(1NEU) mice exhibited normal islet A cells and gut endocrine L cells, and no decrement in pancreatic or intestinal glucagon gene expression. These findings demonstrate that Pax-2 is not essential for the developmental formation of islet A or gut L cells and does not play a role in the physiological control of proglucagon gene expression in vivo.
D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage; D002478:Cells, Cultured; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D007422:Intestines / Q000166:cytology* / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051762:PAX2 Transcription Factor; D010179:Pancreas / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D052336:Proglucagon; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D011498:Protein Precursors; D014157:Transcription Factors; D052336:Proglucagon; D005934:Glucagon