The first two authors contributed equally to this work.
Disruption of the Epilepsy KCNQ2 Gene Results in Neural Hyperexcitability
Article first published online: 25 DEC 2001
Journal of Neurochemistry
Volume 75, Issue 1, pages 28–33, July 2000
How to Cite
Watanabe, H., Nagata, E., Kosakai, A., Nakamura, M., Yokoyama, M., Tanaka, K. and Sasai, H. (2000), Disruption of the Epilepsy KCNQ2 Gene Results in Neural Hyperexcitability. Journal of Neurochemistry, 75: 28–33. doi: 10.1046/j.1471-4159.2000.0750028.x
Abbreviations used : BFNC, benign familial neonatal convulsion ; dpc, days postcoitus ; ES, embryonic stem ; PTZ, pentylenetetrazole.
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Benign familial neonatal convulsion;
- Knockout mouse
Abstract : Benign familial neonatal convulsion (BFNC) is a common idiopathic epilepsy with autosomal dominant inheritance. Recently, two novel voltage-dependent potassium channel genes, KCNQ2 and KCNQ3, were identified by positional cloning as being responsible for BFNC. Heterotetramers of the products of these genes form M-channels and regulate the threshold of electrical excitability of neurons. We disrupted the mouse KCNQ2 gene via gene targeting to study the relationship between KCNQ2 and epilepsy. Homozygous pups (KCNQ2 -/-) died within a few hours after birth owing to pulmonary atelectasis that was not due to the status of epileptic seizures, although their development was morphologically normal. Heterozygous mice had decreased expression of KCNQ2 and showed hypersensitivity to pentylenetetrazole, an inducer of seizure. These data indicate that the decreased expression of KCNQ2 might cause a hyperexcitability of the CNS, which accounts for the mechanism of BFNC.