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Conditional inactivation of the murine serum response factor in the pancreas leads to severe pancreatitis

Francisco Miralles1, Sophie Hebrard, Luciane Lamotte

  • 1Departement de Génétique et Développement, Institut Cochin, INSERM U567, CNRS UMR8104, Université René Descartes Paris V, Paris, France. miralles@cochin.inserm.fr

Laboratory Investigation; a Journal of Technical Methods and Pathology
|August 9, 2006
PubMed

Insights

Serum Response Factor (SRF) is essential for exocrine pancreas maintenance post-weaning. Its disruption causes severe pancreatitis, highlighting SRF

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Gastroenterology

Background:

  • Serum Response Factor (SRF) is a transcription factor involved in cell differentiation, growth, and death.
  • SRF plays a role in various signaling pathways.
  • SRF expression is observed in the developing and adult pancreas.

Purpose of the Study:

  • To investigate the role of SRF in pancreas development and function.
  • To generate and analyze mice with conditional disruption of the Srf gene in the pancreas.

Main Methods:

  • Generation of conditional Srf knockout mice.
  • Analysis of pancreatic development and morphology post-weaning.
  • Assessment of exocrine and endocrine pancreas integrity and function.

Main Results:

  • SRF is dispensable for normal pancreas development (ontogenesis).
  • Conditional Srf disruption in mice leads to severe exocrine pancreas destruction post-weaning, resembling pancreatitis.
  • Massive acinar injury, NF-κB activation, and cytokine release contribute to exocrine pancreas destruction.
  • Endocrine islet organization and function remain preserved despite exocrine damage.

Conclusions:

  • SRF is crucial for maintaining exocrine pancreas integrity after development.
  • Conditional Srf disruption creates a novel spontaneous pancreatitis model.
  • This model offers insights into pancreatitis physiopathology and potential therapeutic targets.

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