ClC 7

Summary

Gene Symbol: ClC 7
Description: chloride channel, voltage-sensitive 7
Alias: ClC-7, D17Wsu51e, H(+)/Cl(-) exchange transporter 7, chloride channel 7 alpha subunit, chloride channel protein 7
Species: mouse
Products:     ClC 7

Top Publications

  1. Lange P, Wartosch L, Jentsch T, Fuhrmann J. ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature. 2006;440:220-3 pubmed
    ..3). The finding that grey-lethal mice, just like ClC-7-deficient mice, show lysosomal storage and neurodegeneration in addition to osteopetrosis implies a more general importance for ClC-7-Ostm1 complexes. ..
  2. Weinert S, Jabs S, Supanchart C, Schweizer M, Gimber N, Richter M, et al. Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation. Science. 2010;328:1401-3 pubmed publisher
    ..This conductance was even deleterious in Clcn7(+/unc) mice. Clcn7(-/-) and Clcn7(unc/unc) mice accumulated less Cl- in lysosomes than did wild-type mice. Thus, lowered lysosomal chloride may underlie their common phenotypes. ..
  3. Kornak U, Kasper D, Bösl M, Kaiser E, Schweizer M, Schulz A, et al. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell. 2001;104:205-15 pubmed
    ..We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane. ..
  4. Kasper D, Planells Cases R, Fuhrmann J, Scheel O, Zeitz O, Ruether K, et al. Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J. 2005;24:1079-91 pubmed
    ..There are important medical implications as defects in the H(+)-ATPase and ClC-7 can underlie human osteopetrosis...
  5. Jentsch T. Chloride and the endosomal-lysosomal pathway: emerging roles of CLC chloride transporters. J Physiol. 2007;578:633-40 pubmed
    ..Surprisingly, ClC-4 and ClC-5 (and probably ClC-3) do not function as Cl- channels, but rather as electrogenic Cl--H+ exchangers. This hints at an important role for luminal chloride in the endosomal-lysosomal system. ..
  6. Neutzsky Wulff A, Karsdal M, Henriksen K. Characterization of the bone phenotype in ClC-7-deficient mice. Calcif Tissue Int. 2008;83:425-37 pubmed publisher
    ..In summary, we present evidence supporting a pivotal role for ClC-7 in acidification of the resorption lacuna and evidence indicating that bone formation and bone resorption are no longer balanced in ClC-7(-/-) mice. ..
  7. Wartosch L, Fuhrmann J, Schweizer M, Stauber T, Jentsch T. Lysosomal degradation of endocytosed proteins depends on the chloride transport protein ClC-7. FASEB J. 2009;23:4056-68 pubmed publisher
    ..These experiments demonstrate that lysosomal pathology is a cell-autonomous consequence of ClC-7 disruption and that ClC-7 is important for lysosomal protein degradation. ..
  8. Lu X, Rios H, Jiang B, Xing L, Kadlcek R, Greenfield E, et al. A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots. Eur J Oral Sci. 2009;117:625-35 pubmed publisher
    ..Genetic mapping has narrowed down the location of the mutant allele to a genetic interval of 3.2 cM on mouse chromosome 17...
  9. Steinberg B, Huynh K, Brodovitch A, Jabs S, Stauber T, Jentsch T, et al. A cation counterflux supports lysosomal acidification. J Cell Biol. 2010;189:1171-86 pubmed publisher
    ..We conclude that cations, in addition to chloride, can support lysosomal acidification and defects in lysosomal anion conductance cannot explain the impaired microbicidal capacity of CF phagocytes...

More Information

Publications26

  1. Meadows N, Sharma S, Faulkner G, Ostrowski M, Hume D, Cassady A. The expression of Clcn7 and Ostm1 in osteoclasts is coregulated by microphthalmia transcription factor. J Biol Chem. 2007;282:1891-904 pubmed
  2. Shevchuk A, Novak P, Taylor M, Diakonov I, Ziyadeh Isleem A, Bitoun M, et al. An alternative mechanism of clathrin-coated pit closure revealed by ion conductance microscopy. J Cell Biol. 2012;197:499-508 pubmed publisher
    ..This technique now enables direct spatial and temporal correlation between functional molecule-specific fluorescence and structural information to follow key biological processes at cell surfaces. ..
  3. Majumdar A, Capetillo Zarate E, Cruz D, Gouras G, Maxfield F. Degradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes. Mol Biol Cell. 2011;22:1664-76 pubmed publisher
    ..Our findings suggest a novel mechanism of lysosomal pH regulation in activated microglia that is required for fA? degradation. ..
  4. Caetano Lopes J, Lessard S, Hann S, Espinoza K, Kang K, Lim K, et al. Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease. Bone. 2017;105:253-261 pubmed publisher
    ..Our results suggest that the benefits of IFN-G therapy in patients with Albers-Schönberg disease may be mutation-specific. ..
  5. Kornak U, Bösl M, Kubisch C. Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes(1). Biochim Biophys Acta. 1999;1447:100-6 pubmed
    ..Moreover, no significant gene structure homology to other members of the CLC family could be detected indicating a great structural diversity of mammalian CLC genes. ..
  6. Weinert S, Jabs S, Hohensee S, Chan W, Kornak U, Jentsch T. Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions. EMBO Rep. 2014;15:784-91 pubmed publisher
    ..Our in vivo structure-function analysis of ClC-7 reveals that both protein-protein interactions and ion transport must be considered in the pathogenesis of ClC-7-related diseases. ..
  7. Pressey S, O Donnell K, Stauber T, Fuhrmann J, Tyynelä J, Jentsch T, et al. Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1. J Neuropathol Exp Neurol. 2010;69:1228-46 pubmed publisher
  8. Rajan I, Read R, Small D, Perrard J, Vogel P. An alternative splicing variant in Clcn7-/- mice prevents osteopetrosis but not neural and retinal degeneration. Vet Pathol. 2011;48:663-75 pubmed publisher
  9. Wen X, Lacruz R, Paine M. Dental and Cranial Pathologies in Mice Lacking the Cl(-) /H(+) -Exchanger ClC-7. Anat Rec (Hoboken). 2015;298:1502-8 pubmed publisher
    ..These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis. ..
  10. Alam I, McQueen A, Acton D, Reilly A, Gerard O Riley R, Oakes D, et al. Phenotypic severity of autosomal dominant osteopetrosis type II (ADO2) mice on different genetic backgrounds recapitulates the features of human disease. Bone. 2017;94:34-41 pubmed publisher
    ..These mouse models will help us to identify genes/factors that influence severity and penetrance of ADO2, and test innovative therapies to treat this disease. ..
  11. Supanchart C, Wartosch L, Schlack C, Kühnisch J, Felsenberg D, Fuhrmann J, et al. ClC-7 expression levels critically regulate bone turnover, but not gastric acid secretion. Bone. 2014;58:92-102 pubmed publisher
    ..ClC-7 does not appear to be crucially involved in gastric acid secretion, which explains the absence of an osteopetrorickets phenotype in CLCN7-related osteopetrosis. ..
  12. Arnaiz I, Johnson M, Cook D, Day M. Changing expression of chloride channels during preimplantation mouse development. Reproduction. 2013;145:73-84 pubmed publisher
    ..Inhibition of the DIDS-sensitive current and the DIDS-insensitive current, with 9-AC, prevented blastocyst expansion. ..
  13. Guo J, Bervoets T, Henriksen K, Everts V, Bronckers A. Null mutation of chloride channel 7 (Clcn7) impairs dental root formation but does not affect enamel mineralization. Cell Tissue Res. 2016;363:361-70 pubmed publisher
    ..We concluded that ClC-7 is essential for osteoclasts to resorb craniofacial bones to enable tooth eruption and root development. Disruption of Clcn7 reduces bone and dentin mineral density but does not affect enamel mineralization. ..
  14. Alam I, Gray A, Chu K, Ichikawa S, Mohammad K, Capannolo M, et al. Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models. Bone. 2014;59:66-75 pubmed publisher
    ..Considerable variability is observed in the heterozygous mice according with the mouse background, suggesting that modifier genes could influence the penetrance of the disease gene. ..
  15. Neutzsky Wulff A, Sims N, Supanchart C, Kornak U, Felsenberg D, Poulton I, et al. Severe developmental bone phenotype in ClC-7 deficient mice. Dev Biol. 2010;344:1001-10 pubmed publisher
    ..Bone formation paremeters were reduced; however, bone formation and mineralization were found to be heterogenous and continuing. ..
  16. Pandruvada S, Beauregard J, Benjannet S, Pata M, Lazure C, Seidah N, et al. Role of Ostm1 Cytosolic Complex with Kinesin 5B in Intracellular Dispersion and Trafficking. Mol Cell Biol. 2016;36:507-21 pubmed publisher
    ..These Ostm1 molecular and cellular functions could elucidate all of the pathophysiologic mechanisms underlying the wide phenotypic spectrum of Ostm1-deficient mice. ..
  17. Wang H, Pan M, Ni J, Zhang Y, Zhang Y, Gao S, et al. ClC-7 Deficiency Impairs Tooth Development and Eruption. Sci Rep. 2016;6:19971 pubmed publisher
    ..We conclude that ClC-7 may affect tooth development by directly targeting tooth cells, and regulate tooth eruption through DFC mediated osteoclast pathway. ..