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 E Sarvetnick

Research output: Contribution to journalArticle

4 Citations (Scopus)

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
StatePublished - Nov 11 2000
Externally publishedYes

Fingerprint

Interferons
Pancreas
Transcription Factors
Transgenes
Regeneration
Knockout Mice
Transgenic Mice
Epithelial Cells
Mutation
Genes

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

IFN-γ overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death. / Krakowski, Michelle; Yeung, Brian; Abdelmalik, Robin; Good, Augusta; Mocnik, Lorraine; Sosa-Pineda, Beatriz; St-Onge, Luc; Gruss, Peter; Sarvetnick, Nora E.

In: Pancreas, Vol. 21, No. 4, 11.11.2000, p. 399-406.

Research output: Contribution to journalArticle

Krakowski, M, Yeung, B, Abdelmalik, R, Good, A, Mocnik, L, Sosa-Pineda, B, St-Onge, L, Gruss, P & Sarvetnick, NE 2000, 'IFN-γ overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death', Pancreas, vol. 21, no. 4, pp. 399-406. https://doi.org/10.1097/00006676-200011000-00011
Krakowski, Michelle ; Yeung, Brian ; Abdelmalik, Robin ; Good, Augusta ; Mocnik, Lorraine ; Sosa-Pineda, Beatriz ; St-Onge, Luc ; Gruss, Peter ; Sarvetnick, Nora E. / IFN-γ overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death. In: Pancreas. 2000 ; Vol. 21, No. 4. pp. 399-406.
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