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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

Authors

  • Kornak U
  • Kasper D
  • Bösl MR
  • Kaiser E
  • Schweizer M
  • Schulz A
  • Friedrich W
  • Delling G
  • Jentsch TJ

Journal

Cell

Publication Data

January 26, 2001

Associated Grants

None

Mesh Terms

  • 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