Pathogenesis of Anorectal Malformations in Retinoic Acid Receptor Knockout Mice Studied by HREM.
Fiche publication
Date publication
juin 2021
Journal
Biomedicines
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HERAULT Yann, Dr TELETIN Marius, Dr VONESCH Jean-Luc, Dr MARK Manuel
Tous les auteurs :
Mark M, Teletin M, Wendling O, Vonesch JL, Féret B, Hérault Y, Ghyselinck NB
Lien Pubmed
Résumé
Anorectal malformations (ARMs) are relatively common congenital abnormalities, but their pathogenesis is poorly understood. Previous gene knockout studies indicated that the signalling pathway mediated by the retinoic acid receptors (RAR) is instrumental to the formation of the anorectal canal and of various urogenital structures. Here, we show that simultaneous ablation of the three RARs in the mouse embryo results in a spectrum of malformations of the pelvic organs in which anorectal and urinary bladder ageneses are consistently associated. We found that these ageneses could be accounted for by defects in the processes of growth and migration of the cloaca, the embryonic structure from which the anorectal canal and urinary bladder originate. We further show that these defects are preceded by a failure of the lateral shift of the umbilical arteries and propose vascular abnormalities as a possible cause of ARM. Through the comparisons of these phenotypes with those of other mutant mice and of human patients, we would like to suggest that morphological data may provide a solid base to test molecular as well as clinical hypotheses.
Mots clés
Fraser syndrome, congenital malformations, mesenteric artery, mouse embryonic development, umbilical artery, vitamin A deficiency
Référence
Biomedicines. 2021 Jun 28;9(7):