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

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

C2 - 25663454

AN - SCOPUS:84936985911

VL - 298

SP - 1502

EP - 1508

JO - Anatomical Record

JF - Anatomical Record

SN - 1932-8486

IS - 8

ER -