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| Item Type: | Article |
|---|---|
| Title: | Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6 |
| Creators Name: | Poet, M., Kornak, U., Schweizer, M., Zdebik, A.A., Scheel, O., Hoelter, S., Wurst, W., Schmitt, A., Fuhrmann, J.C., Planells-Cases, R., Mole, S.E., Huebner, C.A. and Jentsch, T.J. |
| Abstract: | Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6(-/-) neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease. |
| Keywords: | Acidification, Anion transport, Batten disease, Channelopathy, Kuf's disease, Animals, Mice |
| Source: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Volume: | 103 |
| Number: | 37 |
| Page Range: | 13854-13859 |
| Date: | 12 September 2006 |
| Official Publication: | https://doi.org/10.1073/pnas.0606137103 |
| PubMed: | View item in PubMed |
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