Referenced in: none

Automatically associated channels: ClC4 , ClC7

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

Authors: U Kornak, D Kasper, M R Bösl, E Kaiser, M Schweizer, A Schulz, W Friedrich, G Delling, T J Jentsch

Journal, date & volume: Cell, 2001 Jan 26 , 104, 205-15

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11207362

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.