{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:18:39Z","timestamp":1792757919300,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,9,12]]},"abstract":"<jats:p>\n                    Mammalian CLC proteins function as Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels or as electrogenic Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:italic>\n                      Clcn6\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    neurons appeared normal.\n                    <jats:italic>CLCN6<\/jats:italic>\n                    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\n                    <jats:italic>CLCN6<\/jats:italic>\n                    in that disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0606137103","type":"journal-article","created":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T20:48:35Z","timestamp":1157143715000},"page":"13854-13859","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":183,"title":["Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6"],"prefix":"10.1073","volume":"103","author":[{"given":"Mallorie","family":"Po\u00ebt","sequence":"first","affiliation":[{"name":"*Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4t Hamburg, Falkenried 94, D-20246 Hamburg, 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