Conditional inactivation of the murine serum response factor in the pancreas leads to severe pancreatitis.
The Serum Response Factor (SRF) is widely expressed transcription factor acting at the confluence of multiple signaling pathways and has been implicated in the control of differentiation, growth, and cell death. In the present study, we found that SRF is expressed in the developing and adult pancreas. To explore the possible role of SRF in this organ, we have generated mutant mice with conditional disruption of the Srf gene. Such mutants presented normal development of both the exocrine and endocrine pancreas indicating that SRF is dispensable for pancreas ontogenesis. However, after weaning, these mice developed profound morphological alterations of the exocrine pancreas, which were reminiscent of severe pancreatitis. In these mice, massive acinar injury, Nuclear Factor Kappa B activation and proinflammatory cytokines release led to complete destruction of the exocrine pancreas and its replacement by adipose tissue. Despite these changes, the organization and function of the endocrine islets of Langerhans remained well-preserved. This new animal model of spontaneous pancreatitis could prove a valuable tool to gain further insight into the physiopathology of this disease.
Miralles
Francisco
F
Departement de Génétique et Développement, Institut Cochin, INSERM U567, CNRS UMR8104, Université René Descartes Paris V, Paris, France. miralles@cochin.inserm.fr
Hebrard
Sophie
S
Lamotte
Luciane
L
Durel
Beatrice
B
Gilgenkrantz
Helene
H
Li
Zhenlin
Z
Daegelen
Dominique
D
Tuil
David
D
Joshi
Rajiv L
RL
D000818:Animals; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D026362:Serum Response Factor / Q000235:genetics* / Q000502:physiology*
D016328:NF-kappa B; D026362:Serum Response Factor