ABSTRACTClC‐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. Anat Rec, 298:1502–1508, 2015. © 2015 Wiley Periodicals, Inc.