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

Mol Endocrinol. 2002 Oct;16(10):2349-59. doi: 10.1210/me.2002-0149.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Lineage
  • Cells, Cultured
  • Cricetinae
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enteroendocrine Cells / metabolism
  • Gene Expression Regulation
  • Glucagon / genetics*
  • Glucagon / metabolism
  • Homozygote
  • Intestines / cytology*
  • Intestines / physiology
  • Islets of Langerhans / metabolism
  • Kidney / cytology
  • Kidney / metabolism
  • Mice
  • Mice, Transgenic
  • PAX2 Transcription Factor
  • Pancreas / cytology*
  • Pancreas / embryology
  • Pancreas / physiology
  • Proglucagon
  • Promoter Regions, Genetic*
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • Protein Precursors
  • Transcription Factors
  • Proglucagon
  • Glucagon