Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man |
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Authors: | Kornak U Kasper D Bösl M R Kaiser E Schweizer M Schulz A Friedrich W Delling G Jentsch T J |
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Affiliation: | Zentrum für Molekulare Neurobiologie Hamburg, ZMNH, Universit?t Hamburg, D-20246, Hamburg, Germany. |
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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. |
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