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

By U. Kornak, D. Kasper, M. Bösl, E. Kaiser, M. Schweizer, A. Schulz, Wilhelm Friedrich, G. Delling, T. Jentsch. Cell, 2001

997 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/757a571a6c45dc5118b929a7e3f1ade273bfffff

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Citations in the corpus

The vacuolar (H+)-ATPases — nature's most versatile proton pumps (2002, background): “Interestingly, disruption of the chloride channel protein 7 ( CLC-7) gene blocks acid secretion by osteoclasts, leading to OSTEOPETROSIS”
Electrolyte transport in the mammalian colon: mechanisms and implications for disease. (2002, neutral): “Bartter’s syndrome, and myotonias (300, 333, 462, 568).”
Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. (2000, background): “Acid secretion by osteoclasts has been an interesting therapeutic target since the discovery that this process is controlled by the a3 subunit of the V-ATPase and ClC-7, both of which are quite specific to osteoclasts (37, 39, 56).”