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| CLCN7SummaryGene Symbol: CLCN7 Description: chloride channel, voltage-sensitive 7 Alias: CLC-7, CLC7, OPTA2, OPTB4, PPP1R63, H(+)/Cl(-) exchange transporter 7, chloride channel 7 alpha subunit, chloride channel protein 7, protein phosphatase 1, regulatory subunit 63 Species: human Top Publications
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ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel familyS Brandt
Center for Molecular Neurobiology Hamburg, ZMNH, Hamburg University, Germany
FEBS Lett 377:15-20. 1995..Hydropathy analysis indicates that domain D4 cannot serve as a transmembrane domain. Both ClC-6 and ClC-7 cannot be expressed as chloride channels in Xenopus oocytes, either singly or in combination...- Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosisAnnalisa Frattini
Istituto di Tecnologie Biomediche, CNR, Milan, Italy
J Bone Miner Res 18:1740-7. 2003..patients presenting with a severe clinical picture and diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them had the expected two recessive mutations... - Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type IISteven G Waguespack
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
J Bone Miner Res 18:1513-8. 2003..In 11 of 12 kindreds, five different missense mutations were identified in the ClCN7 gene, indicating the genetic basis and possible dominant negative mechanism for ADO2. - ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal functionPhilipp F Lange
Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Universitat Hamburg, Falkenried 94, D 20246 Hamburg, Germany
Nature 440:220-3. 2006..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... - Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosisAna Belinda Campos-Xavier
Department of Medical Genetics and INSERM U393, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
Hum Genet 112:186-9. 2003..of autosomal recessive malignant osteopetrosis have been ascribed to mutations in the chloride channel 7 gene (CLCN7), which accounts for all autosomal dominant type II cases reported to date... 
Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type IIKim Henriksen
Nordic Bioscience, Herlev, Denmark
Am J Pathol 164:1537-45. 2004Autosomal dominant osteopetrosis II (ADOII) is a relatively benign disorder caused by a missense mutation in the ClCN7 gene...- Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel geneE Cleiren
Department of Medical Genetics, University of Antwerp, Belgium
Hum Mol Genet 10:2861-7. 2001..3, we now report seven different mutations in the gene encoding the ClCN7 chloride channel in all 12 ADO II families analysed... - Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and manU Kornak
Zentrum fur Molekulare Neurobiologie Hamburg, ZMNH, Universitat Hamburg, D 20246, Hamburg, Germany
Cell 104:205-15. 2001..We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis... - Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutationSteven G Waguespack
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M D Anderson Cancer Center, 1400 Holcombe Blvd, Unit 435, Houston, Texas 77030, USA
J Clin Endocrinol Metab 92:771-8. 2007..osteopetrosis (ADO) is a sclerosing bone disorder caused by heterozygous mutations in the chloride channel 7 (ClCN7) gene... 
Characteristics of ClC7 Cl- channels and their inhibition in mutant (G215R) associated with autosomal dominant osteopetrosis type II in native osteoclasts and hClcn7 gene-expressing cellsHiroshi Kajiya
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Tamura 2 15 1, Sawara ku, Fukuoka, 8140193, Japan
Pflugers Arch 458:1049-59. 2009ClC7 Cl(-) channels (Clcn7) are crucial for osteoclastic bone resorption and have heterozygous mutation in autosomal osteopetrosis type II (ADO II) patients...- The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomesAustin R Graves
Membrane Transport Biophysics Unit, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Building 35, MSC 3701, Bethesda, Maryland 20892, USA
Nature 453:788-92. 2008.... - Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7Kim Henriksen
Nordic Bioscience A S, Herlev, Denmark
Biochem Biophys Res Commun 378:804-9. 2009..These data demonstrate that ClC-7 is essential for bone resorption, via its role in acidification of the lysosomes and resorption lacunae in osteoclasts... - Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disordersMichael P Whyte
Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St Louis, MO 63131 3597, USA
J Bone Miner Res 25:2515-26. 2010..Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts... - Intracellular ClC-3 chloride channels promote bone resorption in vitro through organelle acidification in mouse osteoclastsFujio Okamoto
Dept of Physiological Science and Molecular Biology, Fukuoka Dental College, 2 15 1 Tamura, Sawara ku, Fukuoka 814 0193, Japan
Am J Physiol Cell Physiol 294:C693-701. 2008..channels expressed in osteoclasts are important for bone resorption since it has been shown that disruption of the ClCN7 gene in mice leads to severe osteopetrosis... - Genetic diseases of acid-base transportersSeth L Alper
Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine and Cell Biology, Harvard Medical School Boston, Massachusetts 02215, USA
Annu Rev Physiol 64:899-923. 2002..Study of acid-base transport disease-associated mutations should enhance our understanding of protein structure-function relationships and their impact on the physiology of cell, tissue, and organism... - Are nonresorbing osteoclasts sources of bone anabolic activity?Morten A Karsdal
Nordic Bioscience A S, Herlev, Denmark
J Bone Miner Res 22:487-94. 2007..Finally, we describe the likely possibility that bone resorption can be attenuated pharmacologically without the undesirable reduction in bone formation... - Neurological aspects of osteopetrosisC G Steward
BMT Unit, Royal Hospital for Children, Bristol, UK
Neuropathol Appl Neurobiol 29:87-97. 2003..of vacuolar-type H(+)-ATPase, encoded by the gene variously termed ATP6i or TCIRG1] or the ClC-7 chloride channel (ClCN7 gene). These pumps are responsible for acidifying the bone surface beneath the osteoclast... - Bone resorption inhibitor alendronate normalizes the reduced bone thickness of TRPV5(-/-) miceTom Nijenhuis
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands
J Bone Miner Res 23:1815-24. 2008..Thus, TRPV5(-/-) mice are able to rescue the resulting defect in osteoclast-mediated bone resorption, possibly mediated by the long-term hypervitaminosis D or other (non)hormonal compensatory mechanisms... - Severe developmental bone phenotype in ClC-7 deficient miceA V Neutzsky-Wulff
Nordic Bioscience A S, Herlev, DK 2730, Denmark
Dev Biol 344:1001-10. 2010..Bone formation paremeters were reduced; however, bone formation and mineralization were found to be heterogenous and continuing... - Refined genomic localization of the genetic lesion in the osteopetrosis (op) rat and exclusion of three positional and functional candidate genes, Clcn7, Atp6v0c, and Slc9a3r2B Perdu
Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium
Calcif Tissue Int 84:355-60. 2009..Three strong functional candidate genes are within the delineated region. Clcn7 was previously shown to underlie different forms of osteopetrosis, in both human and mice... - DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: standardization of molecular investigations of genetic diseases due to consanguinityChing Wan Lam
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
J Hum Genet 52:98-101. 2007..osteopetrosis, a severe disease causing early infantile death in humans, is caused by mutations in the TCIRG1, CLCN7, or OSTM1 genes... - Severe malignant osteopetrosis caused by a GL gene mutationPaola Quarello
Dipartimento di Scienze Pediatriche, Universita di Torino, Turin, Italy
J Bone Miner Res 19:1194-9. 2004..the T-cell immune-regulator-1 (TCIRG1) gene, which is mutated in >50% of the patients, and the chloride channel 7 (ClCN7) gene, which accounts for approximately 10% of cases... - A family of putative chloride channels from Arabidopsis and functional complementation of a yeast strain with a CLC gene disruptionM Hechenberger
Center for Molecular Neurobiology ZMNH, Hamburg University, Martinistr 52, D 20246 Hamburg, Germany
J Biol Chem 271:33632-8. 1996..This suggests that in Arabidopsis AtCLC-d functions as an intracellular chloride channel... - Lysosomal degradation of endocytosed proteins depends on the chloride transport protein ClC-7Lena Wartosch
Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Centrum für Molekulare Medizin, Robert Rossle Str 10, D 13125 Berlin, Germany
FASEB J 23:4056-68. 2009..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... - Infantile malignant, autosomal recessive osteopetrosis: the rich and the poorAnna Villa
Istituto di Tecnologie Biomediche, CNR, via Cervi 93, Segrate, Italy
Calcif Tissue Int 84:1-12. 2009..and artificially created mouse mutants, but the first five genes identified in human ARO (CA-II, TCIRG1, ClCN7, OSTM1, and PLEKHM1) were all involved in the effector function of mature osteoclasts, being linked to .. - Chloride channels and hepatocellular function: prospects for molecular identificationXinhua Li
Department of Physiology and Biophysics University of Texas Medical Branch, Galveston, Texas 77555 0641, USA
Annu Rev Physiol 64:609-33. 2002.... - Chloride channels and transporters in human corneal epitheliumLin Cao
Department of Dermatology, University of California, Davis, CA 95618, USA
Exp Eye Res 90:771-9. 2010..Those molecules and their distribution may play important roles in maintaining resting Cl(-) fluxes and in regulating Cl(-) flux at corneal wounds, which may be a major contributor to wound electrical signaling... - Human ClC-6 is a late endosomal glycoprotein that associates with detergent-resistant lipid domainsSofie Ignoul
Laboratory of Membrane Transport, Department of Molecular Cell Biology, University of Leuven, Leuven, Belgium
PLoS ONE 2:e474. 2007..In this study we focus on human ClC-6, which is structurally most related to the late endosomal/lysomal ClC-7... - Structure and function of V-ATPases in osteoclasts: potential therapeutic targets for the treatment of osteolysisJ Xu
Molecular Orthopaedic Laboratory, School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
Histol Histopathol 22:443-54. 2007..This review summarizes recent research developments in V-ATPases with particular emphasis on osteoclast biology... - Activation by acidic pH of CLC-7 expressed in oocytes from Xenopus laevisLinda Diewald
Pharmakologisches Institute der Universität Mainz, Mainz, Germany
Biochem Biophys Res Commun 291:421-4. 2002..We therefore suggest that ClC-7 in oocytes is a functional chloride current at acidic pH. Since ClC-7 is also found in neuronal tissues and was upregulated in a rat pain model, we suggest a role of CLC-7 also for nociception and pain... - Chloride and the endosomal-lysosomal pathway: emerging roles of CLC chloride transportersThomas J Jentsch
FMP MDC, Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Zentrum für Molekulare Medizin, Robert Rossle Strasse 10, D 13125 Berlin, FRG
J Physiol 578:633-40. 2007..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... - Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes(1)U Kornak
Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 85, 20246, Hamburg, Germany
Biochim Biophys Acta 1447:100-6. 1999The CLC family of voltage-gated chloride channels comprises nine members in mammals. CLCN6 and CLCN7 belong to a novel, poorly characterized subbranch of this family... - A cation counterflux supports lysosomal acidificationBenjamin E Steinberg
Program in Cell Biology, Hospital for Sick Children, Toronto, Canada M5G 1X8
J Cell Biol 189:1171-86. 2010..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... - Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMBVera M Ripoll
Institute for Molecular Biosciences, Co operative Research Centre for Chronic Inflammatory Diseases, The University of Queensland, St Lucia, QLD 4072, Australia
Gene 413:32-41. 2008..expression during osteoclastogenesis was shown to exhibit similar kinetics to the known MITF targets, acp5 and clcn7. GPNMB expressed in RAW/C4 cells exhibited distinct subcellular distribution at different stages of osteoclast .. - The Arabidopsis central vacuole as an expression system for intracellular transporters: functional characterization of the Cl-/H+ exchanger CLC-7Alex Costa
University of Padova, Via U Bassi 58 B, 35131 Padova, Italy
J Physiol 590:3421-30. 2012..The vacuolar expression system has the potential to become a valuable tool for functional studies on intracellular ion channels and transporters from animal cells... - Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesisRodrigo S Lacruz
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90605, USA
J Bone Miner Res 28:672-87. 2013..Atp6v0d2); ATPase, H(+) transporting, lysosomal V1 subunit B2 (Atp6v1b2); chloride channel, voltage-sensitive 7 (Clcn7); and cathepsin K (Ctsk)... - Cross-talk between TRPML1 channel, lipids and lysosomal storage diseasesNorbert Weiss
Hotchkiss Brain Institute Department of Physiology and Pharmacology University of Calgary Calgary, AB Canada
Commun Integr Biol 5:111-3. 2012..membrane proteins (LMPs, that represent the second class of lysosomal proteins), including the V-type proton (H(+))-ATPase(3) and the chloride ion channel CLC7(4) that pumps protons from the cytosol across the lysosomal membrane. - Clinical review: Genome-wide association studies of skeletal phenotypes: what we have learned and where we are headedYi Hsiang Hsu
Hebrew SeniorLife Institute for Aging Research, 1200 Centre Street, Boston, Massachusetts 02131, USA
J Clin Endocrinol Metab 97:E1958-77. 2012..In addition, the identified genetic determinants may be used to enhance current risk factor profiles... - A homozygous contiguous gene deletion in chromosome 16p13.3 leads to autosomal recessive osteopetrosis in a Jordanian patientAlessandra Pangrazio
UOS IRGB, Milan Unit, CNR, Milan, Italy
Calcif Tissue Int 91:250-4. 2012..Mutations in the CLCN7 gene are responsible not only for a substantial portion of ARO patients but also for other forms of osteopetrosis .. - Long-term survival in infantile malignant autosomal recessive osteopetrosis secondary to homozygous p.Arg526Gln mutation in CLCN7Piranit Nik Kantaputra
Faculty of Dentistry, Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Craniofacial Genetics Laboratory, Chiang Mai University, DENTALAND CLINIC, Chiang Mai, Thailand
Am J Med Genet A 158:909-16. 2012..autosomal recessive osteopetrosis (ARO; OMIM 259700) has been reported to be associated with mutations in TCIRG1, CLCN7, or OSTM1... - The virulence gene and clinical phenotypes of osteopetrosis in the Chinese population: six novel mutations of the CLCN7 gene in twelve osteopetrosis familiesChun Wang
Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People s Hospital Affiliated with Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, China
J Bone Miner Metab 30:338-48. 2012..The entire coding region and adjacent splice sites of the CLCN7, TCIRG1, LRP5 and SOST genes were amplified and directly sequenced... - An alternative splicing variant in Clcn7-/- mice prevents osteopetrosis but not neural and retinal degenerationI Rajan
Lexicon Pharmaceuticals, Pathology Department, The Woodlands, TX 77381 1160, USA
Vet Pathol 48:663-75. 2011The ubiquitously expressed chloride channel 7 (CLCN7) is present within the ruffled border of osteoclasts... - Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture riskEmma L Duncan
University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia
PLoS Genet 7:e1001372. 2011..Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets... - Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activationInsun Song
National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center for Gene Regulation, Brain Korea 21, Chonnam National University Medical School, 5 Hak dong, Dong Ku, Gwangju 501 746, Republic of Korea
FEBS Lett 583:2435-40. 2009..directly to the promoter regions of its target genes and induces expression of various genes, including LTBP3, ClC7, cathepsin K, MMP9, and c-Src, which are key players in bone resorption... - A single-center experience in 20 patients with infantile malignant osteopetrosisEvelina Mazzolari
Department of Pediatrics, University of Brescia, 25123 Brescia, Italy
Am J Hematol 84:473-9. 2009..Mean age at diagnosis was 3.9 months, and mean follow-up was 66.75 months. Mutations in TCIRG1, OSTM1, ClCN7, and TNFRSF11A genes were detected in nine, three, one, and one patients, respectively... - Effect of the release from mechanical stress on osteoclastogenesis in RAW264.7 cellsKenjiro Shibata
Department of Orthodontics, Hokkaido University Graduate School of Dental Medicine, Kita ku, Sapporo 060 8586, Japan
Int J Mol Med 28:73-9. 2011..calcitonin receptor (CTR), ATPase H+ transporting vacuolar proton pump member I (ATP6i), chloride channel-7 (ClC7) and dendritic cell-specific transmembrane protein (DC-STAMP) was decreased with mechanical stress application, and .. - Degradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomesAmitabha Majumdar
Department of Biochemistry and Weill Cornell Medical College, New York, NY 10065, USA
Mol Biol Cell 22:1664-76. 2011..Our findings suggest a novel mechanism of lysosomal pH regulation in activated microglia that is required for fAβ degradation... - Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1Sarah N R Pressey
Pediatric Storage Disorders Laboratory, Department of Neuroscience, Centre for the Cellular Basis of Behavior, Institute of Psychiatry, King s College London, UK
J Neuropathol Exp Neurol 69:1228-46. 2010..NCL mouse models as a guide, we examined neuropathologic alterations in the central nervous system of Clcn6(-/-), Clcn7(-/-), andgl mice. gl mice bear a mutation in Ostm1, the β-subunit critical for Clcn7 function... - Osteopetrosis due to homozygous chloride channel ClCN7 mutation mimicking metabolic disease with haematological and neurological impairmentD Furthner
Department of Paediatrics, Children s Hospital Linz, Linz, Austria
Klin Padiatr 222:180-3. 2010..old male Turkish patient suffering from osteopetrosis caused by a homozygous mutation in the chloride channel gene ClCN7 with developing pancytopenia and severe neurological impairment... - A role for chloride transport in lysosomal protein degradationLena Wartosch
Max Delbrück Centrum für Molekulare Medizin and Leibniz Institut für Molekulare Pharmakologie, Berlin, Germany
Autophagy 6:158-9. 2010..Using novel tissue-specific ClC-7 knockout mice, we have shown that upon loss of ClC-7, lysosomal degradation of endocytosed protein is slowed down and accumulation of autophagosomes occurs... - Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorptionMette G Sørensen
Nordic Bioscience A S, Herlev, Denmark
BMC Musculoskelet Disord 11:250. 2010..To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts... - Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosisShubha R Phadke
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Indian J Med Res 131:508-14. 2010..We investigated the main genetic causes of ARO in eight Indian patients with early postnatal onset and the typical severe clinical course including visual impairment and anaemia... - Sorting motifs of the endosomal/lysosomal CLC chloride transportersTobias Stauber
Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Centrum für Molekulare Medizin, Berlin D 13125, Germany
J Biol Chem 285:34537-48. 2010..The localization of its β-subunit, Ostm1, was determined by that of ClC-7. Ostm1 was not capable of redirecting ClC-7 to lysosomes... - The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cellsHyun Sook Kim
Department of Biomedical Science, College of Health Science, Korea University, Seoul 136 703, Republic of Korea
Int J Mol Med 29:169-77. 2012..osteoclasts by inhibiting osteoclast-associated genes (cathepsin K, MMP-9, CAII, TCIRG1, OSTM1 and CLCN7)... - The late endosomal ClC-6 mediates proton/chloride countertransport in heterologous plasma membrane expressionIoana Neagoe
Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin, D 13125 Berlin, Germany
J Biol Chem 285:21689-97. 2010..Additionally changing the chloride-coordinating serine 157 to proline increased the NO(3)(-) conductance of this mutant. Taken together, these data demonstrate for the first time that ClC-6 is a Cl(-)/H(+) antiporter... - Fine mapping and expression of candidate genes within the chromosome 10 QTL region of the high and low alcohol-drinking ratsPaula J Bice
Department of Medicine, Indiana University School of Medicine, Medical Research and Library Building, Indianapolis, IN 46202, USA
Alcohol 44:477-85. 2010..Quantitative real-time PCR was used to examine mRNA expression of six candidate genes (Crebbp, Trap1, Gnptg, Clcn7, Fahd1, and Mapk8ip3) located within the narrowed QTL region in the HAD1/LAD1 rats... - A newly described mutation of the CLCN7 gene causes neuropathic autosomal recessive osteopetrosis in an Arab familyJumana Y Al-Aama
Department of Genetic Medicine and Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
Clin Dysmorphol 21:1-7. 2012..Preliminary studies suggest that this neuropathic form is more likely to be caused by mutations in the CLCN7 gene in an autosomal recessive manner... - The G215R mutation in the Cl-/H+-antiporter ClC-7 found in ADO II osteopetrosis does not abolish function but causes a severe trafficking defectPatrick Schulz
Department of Biophysical Chemistry, Max Planck Institute of Biophysics, Frankfurt, Germany
PLoS ONE 5:e12585. 2010..It is implied in the pathogenesis of lysosomal storage disease and osteopetrosis. Because of its endosomal/lysosomal localization it is still poorly characterized... - Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulationStefanie Weinert
Leibniz Institut fur Molekulare Pharmakologie FMP, 13125 Berlin, Germany
Science 328:1401-3. 2010..Despite maintaining lysosomal conductance and normal lysosomal pH, these Clcn7(unc/unc) mice showed lysosomal storage disease like mice lacking ClC-7... - Chloride channels regulate chondrogenesis in chicken mandibular mesenchymal cellsMeiyu Tian
Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xi an, Shaanxi 710032, PR China
Arch Oral Biol 55:938-45. 2010..We found that CLCN1 and CLCN3-7 mRNA were expressed in CMMC and NPPB reduced expression of CLCN3, CLCN5, and CLCN7 mRNA in these cells... - CLC-7: a potential therapeutic target for the treatment of osteoporosis and neurodegenerationQingxiao Zhao
College of Chemical Engineering, Northeast Dianli University, Jilin, PR China
Biochem Biophys Res Commun 384:277-9. 2009..In the present review, some of the known features of CLC-7 such as structure, function and its roles in physiological or pathophysiological processes are highlighted... - Linkage of autosomal dominant radial drusen (malattia leventinese) to chromosome 2p16-21E Heon
Hopital Jules Gonin, Lausanne, Switzerland
Arch Ophthalmol 114:193-8. 1996..To identify the chromosomal location of the gene involved in the pathogenesis of autosomal dominant radial drusen (malattia leventinese)... - Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidificationKim Henriksen
Pharmos Bioscience, Nordic Bioscience and Center for Clinical and Basic Research A S, Herlev, Denmark
J Bone Miner Res 21:58-66. 2006.... - Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivoKim Henriksen
Pharmos Bioscience A S, Herlev Hovedgade 207, Herlev, DK 2730, Ribe County Hospital, Esbjerg, and the University Hospital of Copenhagen, Denmark
Am J Pathol 167:1341-8. 2005..We speculate that the mutations causing ADOI alter the osteoblastic phenotype toward a smaller potential for supporting osteoclastogenesis... - Polymorphisms of the CLCN7 gene are associated with BMD in womenUlrika Pettersson
Bone Research Group, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom
J Bone Miner Res 20:1960-7. 2005..show that a common polymorphism causing a valine to methionine amino acid substitution at codon 418 (V418M) in the CLCN7 gene is associated with femoral neck BMD in women... - Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegenerationDagmar Kasper
Zentrum für Molekulare Neurobiologie, Universitat Hamburg, Hamburg, Germany
EMBO J 24:1079-91. 2005..There are important medical implications as defects in the H(+)-ATPase and ClC-7 can underlie human osteopetrosis... - In vitro differentiation of CD14 cells from osteopetrotic subjects: contrasting phenotypes with TCIRG1, CLCN7, and attachment defectsHarry C Blair
Department of Pathology, University of Pittsburgh, Veteran s Affairs Medical Center, Pittsburgh, Pennsylvania 15261, USA
J Bone Miner Res 19:1329-38. 2004..Analysis of genotypes showed that TCIRG1 anomalies correlated with acid transport defects, but surprisingly, organic matrix removal failure correlated with CLCN7 defects; an attachment defect had normal TCIRG1 and CLCN7. - Identification of a novel mutation in the coding region of the grey-lethal gene OSTM1 in human malignant infantile osteopetrosisAlfredo Ramirez
Institut fur Humangenetik, Universitat Bonn, Germany
Hum Mutat 23:471-6. 2004..disorder: TCIRG1, encoding a subunit of the osteoclast H(+)-ATPase, and the voltage-gated chloride channel gene CLCN7. We excluded both genes in a small inbred family with malignant infantile osteopetrosis and undertook linkage .. - Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestationsC Letizia
Department of Clinical Science, Division of Internal Medicine, University of Rome La Sapienza, Rome, Italy
Calcif Tissue Int 74:42-6. 2004..and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic... - Expression of voltage-gated chloride channels in human glioma cellsM L Olsen
Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
J Neurosci 23:5572-82. 2003..This may in turn facilitate rapid changes in cell size and shape as cells divide or invade through tortuous extracellular brain spaces... - Molecular pathology of renal chloride channels in Dent's disease and Bartter's syndromeR V Thakker
Molecular Endocrinology Group, University of Oxford, John Radcliffe Hospital, Headington, Oxford, Oxon, UK
Exp Nephrol 8:351-60. 2000..To date 9 such CLCs (CLC-1 to CLC-7, CLC-Ka and CLC-Kb which are respectively encoded by the genes CLCN1 to CLCN7, CLCNKa and CLCNKb) have been identified in mammals... - Locus heterogeneity of autosomal dominant osteopetrosis (ADO)K E White
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA
J Clin Endocrinol Metab 84:1047-51. 1999..Our results demonstrate that there is locus heterogeneity of this disorder; therefore, mutations in at least two different genes can give rise to the ADO phenotype... - The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosisR V Thakker
Medical Research Council Molecular Endocrinology Group, Medical Research Council Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK
Curr Opin Nephrol Hypertens 7:385-8. 1998..To date nine such voltage-gated CLCs (CLC-1 to CLC-7, CLC-Ka and CLC-Kb, which are encoded by the genes CLCN1 to CLCN7, CLC-Ka and CLC-Kb, respectively) have been identified in mammals... - The exon-intron architecture of human chloride channel genes is not conservedJ Eggermont
Laboratorium voor Fysiologie, Katholieke Universiteit Leuven, Campus Gasthuisberg O and N, B 3000 Leuven, Belgium
Biochim Biophys Acta 1397:156-60. 1998..The corresponding region (3.4 kbp) of the human CLCN7 gene has now been cloned and sequenced... - The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expressionG Lennon
Human Genome Center, Lawrence Livermore National Laboratory, Livermore, California 94550, USA
Genomics 33:151-2. 1996 - Polymorphisms in the CLCN7 gene modulate bone density in postmenopausal women and in patients with autosomal dominant osteopetrosis type IIU Kornak
Max Planck Institute for Molecular Genetics and Institute for Medical Genetics, Charite University Hospital, D 13353 Berlin, Germany
J Clin Endocrinol Metab 91:995-1000. 2006..The fact that mutations in the ClC-7 chloride channel cause autosomal dominant osteopetrosis (ADOII) make the CLCN7 gene an attractive candidate for the regulation of bone density. - Expression of mouse osteoclast K-Cl Co-transporter-1 and its role during bone resorptionHiroshi Kajiya
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Tamura, Japan
J Bone Miner Res 21:984-92. 2006..DIOA also decreased Cl- extrusion and reduced H+ extrusion activity. These results show that KCC1 provides a Cl- extrusion mechanism accompanying the H+ extrusion during bone resorption... - Mutations in OSTM1 (grey lethal) define a particularly severe form of autosomal recessive osteopetrosis with neural involvementAlessandra Pangrazio
Institute for Biomedical Technologies, CNR, Milan, Italy
J Bone Miner Res 21:1098-105. 2006..This defect is also present in the gl mouse, which could represent a good model to study the role of the gene in the pathogenesis of this disease... - Identification of the CLCN7 gene mutations in two Chinese families with autosomal dominant osteopetrosis (type II)Zhen Lin Zhang
The Department of Osteoporosis, Osteoporosis Research Unit, Shanghai Jiao Tong University Affiliated Sixth People s Hospital, Shanghai, 600 Yi Shan Rd, Shanghai, 200233, People s Republic of China
J Bone Miner Metab 27:444-51. 2009..Recent studies have reported loss-of-function mutations in the chloride channel 7 (CLCN7) gene as a cause of autosomal dominant osteopetrosis type II (ADO-II)... - NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclastsHideyuki Sasaki
Departments of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
J Med Invest 56:33-41. 2009..Our results suggest that RANKL may stimulate switching between Nox homologues during osteoclast differentiation, and Nox-derived ROS may be crucial for RANKL-induced osteoclast differentiation... - A novel CLCN7 mutation resulting in a most severe form of autosomal recessive osteopetrosisNesrin Besbas
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey
Eur J Pediatr 168:1449-54. 2009..are also associated with primary neurodegeneration, retinal atrophy, and lysosomal storage, which are caused by CLCN7 and OSTM1 gene mutations... - Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in miceKaj Josephsen
The Water and Salt Research Center, Faculty of Health Sciences, Department of Dental Pathology, Operative Dentistry and Endodontics, School of Dentistry, and Institute of Anatomy, University of Aarhus, DK 8000 Aarhus C, Denmark
Proc Natl Acad Sci U S A 106:1638-41. 2009..Furthermore, osteoclasts in Ae2-/- mice were dramatically enlarged and fail to form the normal ruffled border facing the lacunae. Thus, Ae2 is likely to be an essential component of the bone resorption mechanism in osteoclasts... - Characterization of the bone phenotype in ClC-7-deficient miceAnita Vibsig Neutzsky-Wulff
Nordic Bioscience A S, Herlev Hovedgade 207, 2730, Herlev, Denmark
Calcif Tissue Int 83:425-37. 2008..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... - Physiological roles of CLC Cl(-)/H (+) exchangers in renal proximal tubulesVanessa Plans
Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Centrum für Molekulare Medizin, Berlin, Germany
Pflugers Arch 458:23-37. 2009..Loss of ClC-7 or its beta-subunit Ostm1 entails lysosomal storage in the PT, in addition to the neuronal lysosomal storage and osteopetrosis that are the hallmarks of ClC-7/Ostm1 loss in mice and men... - Ion transporters involved in acidification of the resorption lacuna in osteoclastsKim Henriksen
Nordic Bioscience A S, Herlev Hovedgade 207, 2730 Herlev, Denmark
Calcif Tissue Int 83:230-42. 2008..Furthermore, a group of other ion transporters, including carbonic anhydrase II, the NHEs, and potassium-chloride cotransporters, are all involved in resorption but do not seem to directly be involved in acidification of the lysosomes... - CLCN7 polymorphisms and bone mineral density in healthy premenopausal white women and in white menKang Chu
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Bone 43:995-8. 2008Mutations in the chloride channel 7 gene (CLCN7) cause osteopetrosis, and polymorphisms of CLCN7 in the non-disease allele are associated with penetrance of the autosomal dominant osteopetrosis (ADO) phenotype... - ClC chloride channels in tooth germ and odontoblast-like MDPC-23 cellsJin Hou
Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xi an, Shaanxi 710032, PR China
Arch Oral Biol 53:874-8. 2008..To detect expression of ClC chloride channel mRNA in tooth germ and odontoblasts, and explore the affect of chloride channel function on cell proliferation and cell cycle... - Genetics, pathogenesis and complications of osteopetrosisAndrea Del Fattore
Department of Experimental Medicine, Via Vetoio Coppito 2, 67100 L Aquila, Italy
Bone 42:19-29. 2008..including the TCIRG1 gene, encoding for the a3 subunit of the H+ATPase and accounting for >50% of cases, the ClCN7 and the OSTM1 genes, which have closely related function and account for approximately 10% of cases, also .. - Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survivalRasmus H Nielsen
Nordic Bioscience A S, Herlev Hovedgade 207, Herlev, DK 2730, Denmark
Biochem Biophys Res Commun 360:834-9. 2007..In summary, we found that acidification leading to calcium release from bone during resorption controls osteoclast survival, potentially explaining the increased numbers of osteoclasts in patients with osteopetrosis... - Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorptionMette G Sørensen
Nordic Bioscience A S, Herlev, Denmark
J Bone Miner Res 22:1640-8. 2007..By testing natural compounds in acidification assays, diphyllin was identified. We characterized diphyllin with respect to the pharmacological effects on osteoclasts... - The expression of Clcn7 and Ostm1 in osteoclasts is coregulated by microphthalmia transcription factorNicholas A Meadows
Institute for Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia
J Biol Chem 282:1891-904. 2007..Microarray analysis identified a set of genes superinduced by MITF overexpression, including Clcn7 (chloride channel 7) and Ostm1 (osteopetrosis-associated transmembrane protein 1)... - Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell linesKenichi Harada
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, TX 75390, USA
Oncogene 21:4345-9. 2002..In five of six cell lines, restoration of RASSF1A mRNA was confirmed by RT-PCR. Our findings indicate that aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many different forms of pediatric tumors... - Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulationMichael Köttgen
Renal Division, University Hospital of Freiburg, Freiburg, Germany
EMBO J 24:705-16. 2005..Furthermore, PACS proteins may represent a novel molecular mechanism for ion channel trafficking, directing acidic cluster-containing ion channels to distinct subcellular compartments... - The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosisQing Yang Huang
Department of Medicine, The University of Hong Kong, Hong Kong
Bone 45:289-94. 2009..We sought to determine whether the allelic variation in seven monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, TGFB1 and SLC26A2) contributes to osteoporosis/bone mineral density (BMD) variation in ..
Research Grants
- CREATION OF THE AD02 MOUSEMICHAEL ECONS; Fiscal Year: 2007..The disorder usually results from missense mutations in the Chloride Channel 7 gene (CLCN7)...
- PROTEOMICS OF REGULATED EXOCYTOSIS IN OSTEOCLASTSF Ross; Fiscal Year: 2007....
- C1C CHANNELS IN A HOMOGENEOUS EPITHELIUMJOSEPH MINDELL; Fiscal Year: 2002..These studies will dramatically improve our understanding of the role played by ClC channels in normal salt-secretion and will establish a paradigm for the eventual development of drugs to modulate these processes. ..
- Identification of Genes for Alcohol Preference in Noninbred Rats and MicePaula Bice; Fiscal Year: 2009..abstract_text> ..
- TWO X-LINKED GENES THAT REGULATE MINERAL HOMEOSTASISMichael Whyte; Fiscal Year: 2002....