Leukoencephalopathy upon disruption of the chloride channel ClC-2

Judith Blanz, Michaela Schweizer, Muriel Auberson, Hannes Maier, Adrian Muenscher, Christian A. Hübner*, Thomas J. Jentsch

*Corresponding author for this work

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

ClC-2 is a broadly expressed plasma membrane chloride channel that is modulated by voltage, cell swelling, and pH. A human mutation leading to a heterozygous loss of ClC-2 has previously been reported to be associated with epilepsy, whereas the disruption of Clcn2 in mice led to testicular and retinal degeneration. We now show that the white matter of the brain and spinal cord of ClC-2 knock-out mice developed widespread vacuolation that progressed with age. Fluid-filled spaces appeared between myelin sheaths of the central but not the peripheral nervous system. Neuronal morphology, in contrast, seemed normal. Except for the previously reported blindness, neurological deficits were mild and included a decreased conduction velocity in neurons of the central auditory pathway. The heterozygous loss of ClC-2 had no detectable functional or morphological consequences. Neither heterozygous nor homozygous ClC-2 knock-out mice had lowered seizure thresholds. Sequencing of a large collection of human DNA and electrophysiological analysis showed that several ClC-2 sequence abnormalities previously found in patients with epilepsy most likely represent innocuous polymorphisms.

Original languageEnglish (US)
Pages (from-to)6581-6589
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number24
DOIs
StatePublished - Jun 13 2007

Keywords

  • Anion transport
  • Glia
  • Ion siphoning
  • Knock-out
  • Leukodystrophy
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neuroscience(all)

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    Blanz, J., Schweizer, M., Auberson, M., Maier, H., Muenscher, A., Hübner, C. A., & Jentsch, T. J. (2007). Leukoencephalopathy upon disruption of the chloride channel ClC-2. Journal of Neuroscience, 27(24), 6581-6589. https://doi.org/10.1523/JNEUROSCI.0338-07.2007