Leukoencephalopathy upon disruption of the chloride channel ClC-2.
Standard
Leukoencephalopathy upon disruption of the chloride channel ClC-2. / Blanz, Judith; Schweizer, Michaela; Auberson, Muriel; Maier, Hannes; Münscher, Adrian; Hübner, Christian; Jentsch, Thomas J.
In: J NEUROSCI, Vol. 27, No. 24, 24, 2007, p. 6581-6589.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Leukoencephalopathy upon disruption of the chloride channel ClC-2.
AU - Blanz, Judith
AU - Schweizer, Michaela
AU - Auberson, Muriel
AU - Maier, Hannes
AU - Münscher, Adrian
AU - Hübner, Christian
AU - Jentsch, Thomas J
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 27
SP - 6581
EP - 6589
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 24
M1 - 24
ER -
