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Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man

Item Type:Article
Title:Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man
Creators Name:Kornak, U. and Kasper, D. and Boesl, M.R. and Kaiser, E. and Schweizer, M. and Schulz, A. and Friedrich, W. and Delling, G. and Jentsch, T.J.
Abstract:Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl(-) channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is highly expressed in the ruffled membrane, formed by the fusion of H(+)-ATPase-containing vesicles, that secretes protons into the lacuna. We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis. We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane.
Keywords:Adenosine Triphosphatases, CD Antigens, Northern Blotting, Western Blotting, Bone Development, Bone Resorption, Cell Surface Extensions, Cultured Cells, Chloride Channels, Mammalian Embryo, Reporter Genes, Immunohistochemistry, In Situ Hybridization, Integrin beta3, Confocal Microscopy, Nerve Degeneration, Optic Nerve, Organelles, Osteoclasts, Osteopetrosis, Platelet Membrane Glycoproteins, RNA, Recombinant Fusion Proteins, Retina, Retinal Degeneration, DNA Sequence Analysis, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:104
Number:2
Page Range:205-215
Date:26 January 2001
Official Publication:https://doi.org/10.1016/S0092-8674(01)00206-9
PubMed:View item in PubMed

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