The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Clcn3  -  chloride channel 3

Mus musculus

Synonyms: Chloride channel protein 3, Chloride transporter ClC-3, ClC-3, Clc3, H(+)/Cl(-) exchange transporter 3
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Clcn3

  • RESULTS: Together with developmental retardation and higher mortality, the Clcn3-/- mice showed neurological manifestations such as blindness, motor coordination deficit, and spontaneous hyperlocomotion [1].
  • Other characteristics of the Clcn3(-/-) mice included an abnormal gait, kyphosis, and absence of hindlimb escape extension upon tail elevation [2].
  • Clcn3(-/-) mice had normal serum electrolytes and pH, and exhibited neither hyperglycemia nor rebound hypoglycemia following a glucose load [2].
  • Mice lacking the anion channel ClC-3 (Clcn3((-/-))) died from presumed sepsis following intravascular catheter placement, whereas Clcn3((+/+)) littermates survived [3].

High impact information on Clcn3

  • Because ClC-3 is a channel protein belonging to a large gene family of chloride channels, these results indicate that ClC-3 encodes ICl.vol in many native mammalian cells [4].
  • A mutation of asparagine to lysine at position 579 at the end of the transmembrane domains of ClC-3 abolishes the outward rectification and changes the anion selectivity from I- > Cl- to Cl- > I- but leaves swelling activation intact [4].
  • Here we report that functional expression in NIH/3T3 cells of a cardiac clone of another member of the ClC family, ClC-3, results in a large basally active chloride conductance, which is strongly modulated by cell volume and exhibits many properties identical to those of ICl.vol in native cells [4].
  • While swelling-activated currents are unchanged in mice with disrupted ClC-3, acidification of synaptic vesicles is impaired and there is severe postnatal degeneration of the retina and the hippocampus [5].
  • Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus [5].

Biological context of Clcn3

  • Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene [6].
  • CONCLUSIONS: These results indicated that the neurodegeneration observed in the Clcn3-/- mice was caused by an abnormality in the machinery which degrades the cellular protein and was associated with the phenotype of neuronal ceroid lipofuscinosis (NCL) [1].
  • 9. Our results provide direct evidence for involvement of ClC-3 in endosomal acidification by Cl- shunting of the interior-positive membrane potential created by the vacuolar H+ pump [7].
  • These effects were prevented by a protein kinase A (PKA) inhibitor, KT5720, or by mutation of a single consensus protein kinase C (PKC) phosphorylation site (S51A) on the N-terminus of ClC-3, which also mediates PKC inhibition of ICl,ClC-3 [8].
  • Consistent with a normal regulatory volume decrease response, the magnitude and the kinetics of the swell-activated Cl(-) currents in cells from ClC-3-deficient mice were equivalent to those from wild-type mice [6].

Anatomical context of Clcn3


Associations of Clcn3 with chemical compounds

  • Niflumic acid-treated PMNs also had impaired transendothelial migration in vitro, whereas migration in vivo was not altered in Clcn3((-/-)) PMNs [3].
  • Cardiomyocytes derived from ClC-3-deficient mice similarly underwent apoptosis after exposure to staurosporine; moreover, apoptosis was prevented by application of DIDS or NPPB [11].

Other interactions of Clcn3

  • Moreover, the I(ATPCl) magnitude from wild-type animals was comparable to that from mice with null mutations in the Cftr, Clcn3 and Clcn2 Cl- channel genes [12].
  • To clarify whether Cl-/HCO3- exchangers or Cl- channels are targets of DIDS and whether ClC-3 is involved in the apoptotic process, staurosporine-induced reduction of cell viability, DNA laddering and caspase-3 activation were examined in cultured mouse ventricular myocytes derived from wild-type and ClC-3-deficient mice [11].

Analytical, diagnostic and therapeutic context of Clcn3


  1. CLC-3 deficiency leads to phenotypes similar to human neuronal ceroid lipofuscinosis. Yoshikawa, M., Uchida, S., Ezaki, J., Rai, T., Hayama, A., Kobayashi, K., Kida, Y., Noda, M., Koike, M., Uchiyama, Y., Marumo, F., Kominami, E., Sasaki, S. Genes Cells (2002) [Pubmed]
  2. Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels. Dickerson, L.W., Bonthius, D.J., Schutte, B.C., Yang, B., Barna, T.J., Bailey, M.C., Nehrke, K., Williamson, R.A., Lamb, F.S. Brain Res. (2002) [Pubmed]
  3. Anion Channels, Including ClC-3, Are Required for Normal Neutrophil Oxidative Function, Phagocytosis, and Transendothelial Migration. Moreland, J.G., Davis, A.P., Bailey, G., Nauseef, W.M., Lamb, F.S. J. Biol. Chem. (2006) [Pubmed]
  4. Molecular identification of a volume-regulated chloride channel. Duan, D., Winter, C., Cowley, S., Hume, J.R., Horowitz, B. Nature (1997) [Pubmed]
  5. Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Stobrawa, S.M., Breiderhoff, T., Takamori, S., Engel, D., Schweizer, M., Zdebik, A.A., Bösl, M.R., Ruether, K., Jahn, H., Draguhn, A., Jahn, R., Jentsch, T.J. Neuron (2001) [Pubmed]
  6. Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene. Arreola, J., Begenisich, T., Nehrke, K., Nguyen, H.V., Park, K., Richardson, L., Yang, B., Schutte, B.C., Lamb, F.S., Melvin, J.E. J. Physiol. (Lond.) (2002) [Pubmed]
  7. ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation. Hara-Chikuma, M., Yang, B., Sonawane, N.D., Sasaki, S., Uchida, S., Verkman, A.S. J. Biol. Chem. (2005) [Pubmed]
  8. Intracellular cyclic AMP inhibits native and recombinant volume-regulated chloride channels from mammalian heart. Nagasaki, M., Ye, L., Duan, D., Horowitz, B., Hume, J.R. J. Physiol. (Lond.) (2000) [Pubmed]
  9. Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein. Borsani, G., Rugarli, E.I., Taglialatela, M., Wong, C., Ballabio, A. Genomics (1995) [Pubmed]
  10. Chloride and the endosomal-lysosomal pathway: emerging roles of CLC chloride transporters. Jentsch, T.J. J. Physiol. (Lond.) (2007) [Pubmed]
  11. ClC-3-independent sensitivity of apoptosis to Cl- channel blockers in mouse cardiomyocytes. Takahashi, N., Wang, X., Tanabe, S., Uramoto, H., Jishage, K., Uchida, S., Sasaki, S., Okada, Y. Cell. Physiol. Biochem. (2005) [Pubmed]
  12. A novel chloride conductance activated by extracellular ATP in mouse parotid acinar cells. Arreola, J., Melvin, J.E. J. Physiol. (Lond.) (2003) [Pubmed]
  13. Functional and molecular identification of a novel chloride conductance in canine colonic smooth muscle. Dick, G.M., Bradley, K.K., Horowitz, B., Hume, J.R., Sanders, K.M. Am. J. Physiol. (1998) [Pubmed]
WikiGenes - Universities