1. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation
- Author
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Dominik N. Müller, Maria Morawietz, Dominique Bazin, Suzanne Menashi, Alain Schmitt, Jean Marc Massé, Marie Lucile Figueres, Agnès Linglart, Francisco de Assis Rocha Neves, Jianghui Hou, Rosa Vargas-Poussou, Ana Carolina Acevedo, Frédéric Courson, Dominique Le Denmat, Alejandro Garcia-Castaño, Matthias Petzold, Delphine Zenaty, Ariane Berdal, Julia Thumfart, Renato Demontis, Andreas Kiesow, Yong Wu, Maria Cristina Manzanares, Jean Christophe Fricain, Catherine Chaussain, Claire Bardet, Patricia Carvalho-Lobato, Georg Lorenz, Benoit Vallée, Sandy Ribes, Paulo Marcio Yamaguti, Mayssam Khaddam, Brigitte Baroukh, Deborah Talmud, Pascal Houillier, Thomas Guilbert, Benjamin Salmon, Tilman Breiderhoff, and Gaël Y. Rochefort
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Mutation ,Tight junction ,Enamel paint ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Amelogenesis ,Matrix (biology) ,medicine.disease ,medicine.disease_cause ,stomatognathic diseases ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,stomatognathic system ,Internal medicine ,visual_art ,medicine ,visual_art.visual_art_medium ,Orthopedics and Sports Medicine ,Amelogenesis imperfecta ,Ameloblast ,Claudin - 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.
- Published
- 2015
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