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.
authors: Herman Ostrow School of Dentistry of USC, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, USA.
authors: Xin
authors: X
authors: Wen
authors: Department of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, New York, USA.
authors: Rodrigo S
authors: RS
authors: Lacruz
authors: Herman Ostrow School of Dentistry of USC, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, USA.
authors: Michael L
authors: ML
authors: Paine
mesh_terms: D000565:Ameloblasts / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D000566:Amelogenesis; D000818:Animals; D001846:Bone Development; D018118:Chloride Channels / Q000172:deficiency* / Q000235:genetics; D003393:Cranial Sutures / Q000002:abnormalities; D019465:Craniofacial Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003743:Dental Enamel / Q000002:abnormalities; D003804:Dentin / Q000002:abnormalities; D003810:Dentinogenesis; D005838:Genotype; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D012886:Skull / Q000002:abnormalities* / Q000000981:diagnostic imaging; D014070:Tooth / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014071:Tooth Abnormalities / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D018118:Chloride Channels; C490803:Clcn7 protein, mouse
keywords: ameloblast; amelogenesis; biomineralization; chloride channels; craniofacial development; enamel; pH regulation