Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.
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.
Pubmed ID: 11207362 RIS Download
Adenosine Triphosphatases | Animals | Antigens, CD | Blotting, Northern | Blotting, Western | Bone Development | Bone Resorption | Cell Surface Extensions | Cells, Cultured | Chloride Channels | Embryo, Mammalian | Genes, Reporter | Humans | Immunohistochemistry | In Situ Hybridization | Integrin beta3 | Mice | Microscopy, Confocal | Nerve Degeneration | Optic Nerve | Organelles | Osteoclasts | Osteopetrosis | Platelet Membrane Glycoproteins | RNA | Recombinant Fusion Proteins | Retina | Retinal Degeneration | Sequence Analysis, DNA