Dental and Cranial Pathologies in Mice Lacking the Cl<sup>-</sup>/H<sup>+</sup>-Exchanger ClC-7

Xin Wen, Rodrigo Lacruz, Michael L. Paine

Research output: Contribution to journalArticle

Abstract

ClC-7 is a 2Cl<sup>-</sup>/1H<sup>+</sup>-exchanger expressed at late endosomes and lysosomes, as well as the ruffled border of osteoclasts. ClC-7 deficiencies in mice and humans lead to impaired osteoclast function and therefore osteopetrosis. Failure of tooth eruption is also apparent in ClC-7 mutant animals, and this has been attributed to the osteoclast dysfunction and the subsequent defect in alveolar bone resorptive activity surrounding tooth roots. Ameloblasts also express ClC-7, and this study aims to determine the significance of ClC-7 in enamel formation by examining the dentitions of ClC-7 mutant mice. Micro-CT analysis revealed that the molar teeth of 3-week old ClC-7 mutant mice had no roots, and the incisors were smaller than their age-matched controls. Despite these notable developmental differences, the enamel and dentin densities of the mutant mice were comparable to those of the wild-type littermates. Scanning electron microscopy showed normal enamel crystallite and prismatic organization in the ClC-7 mutant mice, although the enamel was thinner (hypoplastic) than in controls. These results suggested that ClC-7 was not critical to enamel and dentin formation, and the observed tooth defects may be related more to a resulting alveolar bone phenotype. Micro-CT analysis also revealed abnormal features in the calvarial bones of the mutant mice. The cranial sutures in ClC-7 mutant mice remained open compared to the closed sutures seen in the control mice at 3 weeks. These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis.

Original languageEnglish (US)
Pages (from-to)1502-1508
Number of pages7
JournalAnatomical Record
Volume298
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint

pathology
enamel
tooth enamel
Tooth
teeth
Pathology
Dental Enamel
mice
mutants
tooth
osteoclasts
Osteoclasts
bone
dentition
micro-computed tomography
Dentition
bones
Dentin
sutures
defect

Keywords

  • Ameloblast
  • Amelogenesis
  • Biomineralization
  • Chloride channels
  • Craniofacial development
  • Enamel
  • PH regulation

ASJC Scopus subject areas

  • Anatomy
  • Histology
  • Ecology, Evolution, Behavior and Systematics
  • Biotechnology

Cite this

Dental and Cranial Pathologies in Mice Lacking the Cl<sup>-</sup>/H<sup>+</sup>-Exchanger ClC-7. / Wen, Xin; Lacruz, Rodrigo; Paine, Michael L.

In: Anatomical Record, Vol. 298, No. 8, 01.08.2015, p. 1502-1508.

Research output: Contribution to journalArticle

@article{9b5a076e5ece42e7ba761ed6d967327c,
title = "Dental and Cranial Pathologies in Mice Lacking the Cl-/H+-Exchanger ClC-7",
abstract = "ClC-7 is a 2Cl-/1H+-exchanger expressed at late endosomes and lysosomes, as well as the ruffled border of osteoclasts. ClC-7 deficiencies in mice and humans lead to impaired osteoclast function and therefore osteopetrosis. Failure of tooth eruption is also apparent in ClC-7 mutant animals, and this has been attributed to the osteoclast dysfunction and the subsequent defect in alveolar bone resorptive activity surrounding tooth roots. Ameloblasts also express ClC-7, and this study aims to determine the significance of ClC-7 in enamel formation by examining the dentitions of ClC-7 mutant mice. Micro-CT analysis revealed that the molar teeth of 3-week old ClC-7 mutant mice had no roots, and the incisors were smaller than their age-matched controls. Despite these notable developmental differences, the enamel and dentin densities of the mutant mice were comparable to those of the wild-type littermates. Scanning electron microscopy showed normal enamel crystallite and prismatic organization in the ClC-7 mutant mice, although the enamel was thinner (hypoplastic) than in controls. These results suggested that ClC-7 was not critical to enamel and dentin formation, and the observed tooth defects may be related more to a resulting alveolar bone phenotype. Micro-CT analysis also revealed abnormal features in the calvarial bones of the mutant mice. The cranial sutures in ClC-7 mutant mice remained open compared to the closed sutures seen in the control mice at 3 weeks. These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis.",
keywords = "Ameloblast, Amelogenesis, Biomineralization, Chloride channels, Craniofacial development, Enamel, PH regulation",
author = "Xin Wen and Rodrigo Lacruz and Paine, {Michael L.}",
year = "2015",
month = "8",
day = "1",
doi = "10.1002/ar.23118",
language = "English (US)",
volume = "298",
pages = "1502--1508",
journal = "Anatomical Record",
issn = "1932-8486",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Dental and Cranial Pathologies in Mice Lacking the Cl-/H+-Exchanger ClC-7

AU - Wen, Xin

AU - Lacruz, Rodrigo

AU - Paine, Michael L.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - ClC-7 is a 2Cl-/1H+-exchanger expressed at late endosomes and lysosomes, as well as the ruffled border of osteoclasts. ClC-7 deficiencies in mice and humans lead to impaired osteoclast function and therefore osteopetrosis. Failure of tooth eruption is also apparent in ClC-7 mutant animals, and this has been attributed to the osteoclast dysfunction and the subsequent defect in alveolar bone resorptive activity surrounding tooth roots. Ameloblasts also express ClC-7, and this study aims to determine the significance of ClC-7 in enamel formation by examining the dentitions of ClC-7 mutant mice. Micro-CT analysis revealed that the molar teeth of 3-week old ClC-7 mutant mice had no roots, and the incisors were smaller than their age-matched controls. Despite these notable developmental differences, the enamel and dentin densities of the mutant mice were comparable to those of the wild-type littermates. Scanning electron microscopy showed normal enamel crystallite and prismatic organization in the ClC-7 mutant mice, although the enamel was thinner (hypoplastic) than in controls. These results suggested that ClC-7 was not critical to enamel and dentin formation, and the observed tooth defects may be related more to a resulting alveolar bone phenotype. Micro-CT analysis also revealed abnormal features in the calvarial bones of the mutant mice. The cranial sutures in ClC-7 mutant mice remained open compared to the closed sutures seen in the control mice at 3 weeks. These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis.

AB - ClC-7 is a 2Cl-/1H+-exchanger expressed at late endosomes and lysosomes, as well as the ruffled border of osteoclasts. ClC-7 deficiencies in mice and humans lead to impaired osteoclast function and therefore osteopetrosis. Failure of tooth eruption is also apparent in ClC-7 mutant animals, and this has been attributed to the osteoclast dysfunction and the subsequent defect in alveolar bone resorptive activity surrounding tooth roots. Ameloblasts also express ClC-7, and this study aims to determine the significance of ClC-7 in enamel formation by examining the dentitions of ClC-7 mutant mice. Micro-CT analysis revealed that the molar teeth of 3-week old ClC-7 mutant mice had no roots, and the incisors were smaller than their age-matched controls. Despite these notable developmental differences, the enamel and dentin densities of the mutant mice were comparable to those of the wild-type littermates. Scanning electron microscopy showed normal enamel crystallite and prismatic organization in the ClC-7 mutant mice, although the enamel was thinner (hypoplastic) than in controls. These results suggested that ClC-7 was not critical to enamel and dentin formation, and the observed tooth defects may be related more to a resulting alveolar bone phenotype. Micro-CT analysis also revealed abnormal features in the calvarial bones of the mutant mice. The cranial sutures in ClC-7 mutant mice remained open compared to the closed sutures seen in the control mice at 3 weeks. These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis.

KW - Ameloblast

KW - Amelogenesis

KW - Biomineralization

KW - Chloride channels

KW - Craniofacial development

KW - Enamel

KW - PH regulation

UR - http://www.scopus.com/inward/record.url?scp=84936985911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936985911&partnerID=8YFLogxK

U2 - 10.1002/ar.23118

DO - 10.1002/ar.23118

M3 - Article

VL - 298

SP - 1502

EP - 1508

JO - Anatomical Record

JF - Anatomical Record

SN - 1932-8486

IS - 8

ER -