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@ARTICLE{Nguyen:285021,
author = {Nguyen, T. N. and Ribes, S. and Andrique, C. and Requin, M.
and Bouchet, J. and Obtel, N. and Slimani, L. and Brouilly,
N. and Torrens, C. and Schmitt, A. and Guilbert, T. and
Morawietz, M. and Kiesow, A. and Brunelle, A. and Percot, A.
and Hadj-Rabia, S. and Gaucher, C. and Le Bivic, A. and
Houillier, P. and Bardet, C. and Muller, D. and Ramirez
Rozzi, F. and Coradin, T. and Breiderhoff, T. and Chaussain,
C.},
title = {{T}he {A}bsence of {C}laudin-10 in the {E}namel {O}rgan
{A}lters {I}ts {I}ntegrity.},
journal = {Journal of dental research},
volume = {105},
number = {3},
issn = {0022-0345},
address = {Thousand Oaks, Calif.},
publisher = {Sage},
reportid = {DZNE-2026-00146},
pages = {385 - 395},
year = {2026},
abstract = {Rare disorders related to tight junction (TJ) proteins have
been associated with amelogenesis imperfecta. Pathogenic
variants of CLDN10, encoding claudin-10b, a cation transport
pore, cause the autosomal recessive HELIX syndrome
(Hypohidrosis, Electrolyte imbalance, hypoLacrymia,
Ichthyosis, Xerostomia). Patients exhibit salivary
dysfunction and rapid enamel wear after tooth eruption.
Since Cldn10 is expressed in the dental epithelium, this
study explores the role of claudin-10b in amelogenesis. We
analyzed amelogenesis in constitutive and conditional Cldn10
knockout (KO) murine models, comparing the findings to human
HELIX enamel. First, analysis of constitutive Cldn10
knockout (KO) mice, which die within a few hours after
birth, showed that claudin-10 is present at the plasma
membrane of the stratum intermedium but not at the TJs
during the secretory stage. Its absence altered gene
expression related to ion transport and pH control, although
without major disturbance in cell polarization or enamel
matrix synthesis. Examination of later stages of
amelogenesis in epithelium-targeted conditional Cldn10 KO
mice showed that claudin-10 is present in the papillary
layer at the maturation stage. In its absence, the pH of the
enamel matrix was more basic during early maturation,
suggesting that claudin-10 determines enamel matrix pH.
However, at later stage of the maturation process, the pH
was corrected and the resulting enamel did not show major
structural or elemental alterations. These later findings
were confirmed by exploring the enamel of Cldn10 KO
transplanted tooth germs, which have developed in a
controlled mineral environment. Nevertheless, higher
contents of aluminum were detected in the enamel of
transplanted germs and in human HELIX enamel, suggesting
that claudin-10 deficiency may lead to a loss of enamel
organ integrity. These data suggest that while salivary
dysfunction is the main cause of enamel wear in HELIX,
claudin-10 plays a direct role in amelogenesis by
determining pH and enamel organ integrity.},
keywords = {Animals / Claudins: genetics / Claudins: physiology /
Claudins: deficiency / Mice, Knockout / Mice / Enamel Organ:
metabolism / Amelogenesis: genetics / Amelogenesis:
physiology / Hydrogen-Ion Concentration / Tight Junctions /
Dental Enamel / Humans / Aluminum (Other) / Ameloblasts
(Other) / Amelogenesis (Other) / Genetic disorders (Other) /
Ion transport (Other) / Tight junctions (Other) / Claudins
(NLM Chemicals) / claudin 10 (NLM Chemicals)},
cin = {AG Wurst},
ddc = {610},
cid = {I:(DE-2719)1140001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40717352},
doi = {10.1177/00220345251349109},
url = {https://pub.dzne.de/record/285021},
}