IFN-γ overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death

Michelle Krakowski, Brian Yeung, Robin Abdelmalik, Augusta Good, Lorraine Mocnik, Beatriz Sosa-Pineda, Luc St-Onge, Peter Gruss, Nora Sarvetnick

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In the presence of interferon-γ (IFN-γ), pancreatic ductal epithelial cells grow continuously, and islets undergo neogenesis. To determine whether these new islets are derived from conventional precursors, we tested whether IFN-γ can complement the loss of transcription factors known to regulate pancreatic development. We analyzed the effect of a transgene on lethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by intercrossing such mice with transgenic mice whose pancreatic cells make IFN-γ (ins-IFN-γ mice). However, IFN-γ expression did not rescue these mice from the lethal mutations, because no homozygous knockout mice carrying the IFN-γ transgene survived, despite the survival of all other hemizygous gene combinations. This outcome demonstrates that the pathway for IFN-γ regeneration requires the participation of Pax4, Pax6, and Pdx-1. We conclude that the striking islet regeneration observed in the ins-IFN-γ NOD strain is regulated by the same transcription factors that control initial pancreatic development.

Original languageEnglish (US)
Pages (from-to)399-406
Number of pages8
JournalPancreas
Volume21
Issue number4
DOIs
Publication statusPublished - Nov 11 2000

    Fingerprint

Keywords

  • Development
  • Homeoprotein
  • IFN-γ
  • Knockout
  • Murine pancreas
  • Pancreatic cell lineage
  • Pancreatic islets
  • Transcription factors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this