| | |  | | | | Record from Web of Science® | | | | | | |
| Loss of the CIC-7 chloride channel leads to osteopetrosis in mice and man |
|
|
| Author(s): Kornak U, Kasper D, Bosl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch TJ |
| Source: CELL Volume: 104 Issue: 2 Pages: 205-215 Published: JAN 26 2001 |
| Times Cited: 319 References: 40 |
| Abstract: Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed CIC-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. CIC-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 CIC-7 provides the chloride conductance required for an efficient proton pumping by the H+-ATPase of the osteoclast ruffled membrane. |
| Document Type: Article |
| Language: English |
| Reprint Address: Jentsch, TJ (reprint author), Univ Hamburg, Zentrum Mol Neurobiol Hamburg, Martinistr 52, D-20246 Hamburg, Germany |
Addresses:
1. Univ Hamburg, Zentrum Mol Neurobiol Hamburg, D-20246 Hamburg, Germany
2. Univ Hamburg, Inst Pathol, Abt Osteopathol, D-20246 Hamburg, Germany
3. Univ Ulm, Univ Kinderklin, D-89075 Ulm, Germany |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 400PB |
| ISSN: 0092-8674 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |