Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Investigation Année : 2009

Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction

Résumé

Intestinal ganglioneuromatosis is a benign proliferation of nerve ganglion cells, nerve fibers, and supporting cells of the enteric nervous system (ENS) that can result in abnormally large enteric neuronal cells (ENCs) in the myenteric plexus and chronic intestinal pseudoobstruction (CIPO). As phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatase that is critical for controlling cell growth, proliferation, and death, we investigated the role of PTEN in the ENS by generating mice with an embryonic, ENC-selective deletion within the Pten locus. Mutant mice died 2 to 3 weeks after birth, with clinical signs of CIPO and hyperplasia and hypertrophy of ENCs resulting from increased activity of the PI3K/PTEN-AKT-S6K signaling pathway. Further analysis revealed that PTEN was only expressed in developing mouse embryonic ENCs from E15.5 and that the rate of ENC proliferation decreased once PTEN was expressed. Specific deletion of the Pten gene in ENCs therefore induced hyperplasia and hypertrophy in the later stages of embryogenesis. This phenotype was reversed by administration of a pharmacological inhibitor of AKT. In some human ganglioneuromatosis forms of CIPO, PTEN expression was found to be abnormally low and S6 phosphorylation increased. Our study thus reveals that loss of PTEN disrupts development of the ENS and identifies the PI3K/PTEN-AKT-S6K signaling pathway as a potential therapeutic target for ganglioneuromatosis forms of CIPO.
Fichier principal
Vignette du fichier
Puig et al - 2009.pdf (5.74 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02543828 , version 1 (15-04-2020)

Identifiants

Citer

Isabel Puig, Delphine Champeval, Pascal de Santa Barbara, Francis Jaubert, Stanislas Lyonnet, et al.. Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction. Journal of Clinical Investigation, 2009, ⟨10.1172/JCI39929⟩. ⟨hal-02543828⟩
38 Consultations
41 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More