Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation - Sorbonne Université Access content directly
Journal Articles Journal of Bone and Mineral Research Year : 2015

Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation

Julia Thumfart
  • Function : Author
Paulo M Yamaguti
  • Function : Author
Tilman Breiderhoff
  • Function : Author
Alejandro Garcia-Castaño
  • Function : Author
Thomas Guilbert
Alain Schmitt
  • Function : Author
Jean-Marc Massé
  • Function : Author
Georg Lorenz
  • Function : Author
Maria Morawietz
  • Function : Author
Jianghui Hou
  • Function : Author
Patricia Carvalho-Lobato
  • Function : Author
Maria Cristina Manzanares
  • Function : Author
Francisco Neves
  • Function : Author
Andreas Kiesow
  • Function : Author
Matthias Petzold
  • Function : Author
Agnes Linglart
Ana Carolina Acevedo
  • Function : Author
Rosa Vargas-Poussou

Abstract

Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients. © 2015 American Society for Bone and Mineral Research.

Dates and versions

hal-01286223 , version 1 (10-03-2016)

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Claire Bardet, Frédéric Courson, Yong Wu, Mayssam Khaddam, Benjamin Salmon, et al.. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation. Journal of Bone and Mineral Research, 2015, 31 (3), pp.498-513. ⟨10.1002/jbmr.2726⟩. ⟨hal-01286223⟩
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