ArticleThe EMBO journal2005
Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration.
Article in The EMBO journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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Who cites it
172 citing papers in PubMed, 364 citations in OpenAlex.
- Ion transport as a determinant of membrane fusion and fission.Nature structural & molecular biology · 2026Review
- The molecular and functional interplay between the osteopetrosis-associated proteins SNX10, OSTM1, and CLC-7 during mouse osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Targeting TMEM175 in Lysosomal Physiology and Human Diseases.Current stem cell research & therapy · 2026Review
- Targeting lysosomal ion channels to overcome cancer treatment resistance: emerging mechanisms and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)PNature structural & molecular biology · 2025Article
- Disruption of ClC-3-mediated 2ClScientific reports · 2025Article
- Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation.Nature communications · 2025Article
- Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.The Journal of cell biology · 2025Article
- The autophagy protein ATG-9 regulates lysosome function and integrity.The Journal of cell biology · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Article
- Delayed vacuolation in mammalian cells caused by hypotonicity and ion loss.Scientific reports · 2024Article
- Proton-activated chloride channel increases endplate porosity and pain in a mouse spine degeneration model.The Journal of clinical investigation · 2024Article
- Review
- Tunable Cytosolic Chloride Indicators for Real-Time Chloride Imaging in Live Cells.bioRxiv : the preprint server for biology · 2024Article
- Effect of Allele-Specific Clcn7Calcified tissue international · 2024Article
- Multisystem disorder associated with a pathogenic variant in CLCN7 in the absence of osteopetrosis.Molecular genetics & genomic medicine · 2024Article
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Chloride Homeostasis Regulates cGAS-STING Signaling.bioRxiv : the preprint server for biology · 2024Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ClC-7 is a chloride channel of late endosomes and lysosomes. In osteoclasts, it may cooperate with H(+)-ATPases in acidifying the resorption lacuna. In mice and man, loss of ClC-7 or the H(+)-ATPase a3 subunit causes osteopetrosis, a disease characterized by defective bone resorption. We show that ClC-7 knockout mice additionally display neurodegeneration and severe lysosomal storage disease despite unchanged lysosomal pH in cultured neurons. Rescuing their bone phenotype by transgenic expression of ClC-7 in osteoclasts moderately increased their lifespan and revealed a further progression of the central nervous system pathology. Histological analysis demonstrated an accumulation of electron-dense material in neurons, autofluorescent structures, microglial activation and astrogliosis. Like in human neuronal ceroid lipofuscinosis, there was a strong accumulation of subunit c of the mitochondrial ATP synthase and increased amounts of lysosomal enzymes. Such alterations were minor or absent in ClC-3 knockout mice, despite a massive neurodegeneration. Osteopetrotic oc/oc mice, lacking a functional H(+)-ATPase a3 subunit, showed no comparable retinal or neuronal degeneration. There are important medical implications as defects in the H(+)-ATPase and ClC-7 can underlie human osteopetrosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.