TY  - JOUR
AU  - Bardet, Claire
AU  - Courson, Frédéric
AU  - Wu, Yong
AU  - Khaddam, Mayssam
AU  - Salmon, Benjamin
AU  - Ribes, Sandy
AU  - Thumfart, Julia
AU  - Yamaguti, Paulo M
AU  - Rochefort, Gael Y
AU  - Figueres, Marie-Lucile
AU  - Breiderhoff, Tilman
AU  - Garcia-Castaño, Alejandro
AU  - Vallée, Benoit
AU  - Le Denmat, Dominique
AU  - Baroukh, Brigitte
AU  - Guilbert, Thomas
AU  - Schmitt, Alain
AU  - Massé, Jean-Marc
AU  - Bazin, Dominique
AU  - Lorenz, Georg
AU  - Morawietz, Maria
AU  - Hou, Jianghui
AU  - Carvalho-Lobato, Patricia
AU  - Manzanares, Maria Cristina
AU  - Fricain, Jean-Christophe
AU  - Talmud, Deborah
AU  - Demontis, Renato
AU  - Neves, Francisco
AU  - Zenaty, Delphine
AU  - Berdal, Ariane
AU  - Kiesow, Andreas
AU  - Petzold, Matthias
AU  - Menashi, Suzanne
AU  - Linglart, Agnes
AU  - Acevedo, Ana Carolina
AU  - Vargas-Poussou, Rosa
AU  - Müller, Dominik
AU  - Houillier, Pascal
AU  - Chaussain, Catherine
TI  - Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.
JO  - Journal of bone and mineral research
VL  - 31
IS  - 3
SN  - 0884-0431
CY  - [Oxford]
PB  - Oxford University Press
M1  - DZNE-2025-00364
SP  - 498 - 513
PY  - 2016
AB  - 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.
KW  - Adult
KW  - Ameloblasts: metabolism
KW  - Ameloblasts: pathology
KW  - Amelogenesis Imperfecta: metabolism
KW  - Amelogenesis Imperfecta: pathology
KW  - Animals
KW  - Child
KW  - Claudins: deficiency
KW  - Claudins: genetics
KW  - Dental Enamel: abnormalities
KW  - Dental Enamel: metabolism
KW  - Dental Enamel: pathology
KW  - Female
KW  - Humans
KW  - Hydrogen-Ion Concentration
KW  - Male
KW  - Mice
KW  - Middle Aged
KW  - Mutation: genetics
KW  - Phenotype
KW  - Syndrome
KW  - Tight Junctions: metabolism
KW  - Young Adult
KW  - AMELOGENESIS IMPERFECTA (AI) (Other)
KW  - FAMILIAL HYPOMAGNESEMIA WITH HYPERCALCIURIA AND NEPHROCALCINOSIS (FHHNC) (Other)
KW  - MMP-20 (Other)
KW  - SECRETORY AMELOBLASTS (Other)
KW  - pH (Other)
KW  - Claudins (NLM Chemicals)
KW  - claudin 16 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26426912
DO  - DOI:10.1002/jbmr.2726
UR  - https://pub.dzne.de/record/276851
ER  -