Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability

Benign familiar 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 clo ning as being responsible for BFNG. Heterotetramers of the products of thes e genes form M-channels and regulate the threshold of electrical excitabili ty of neurons. We disrupted the mouse KCNQ2 gene via gene targeting to stud y 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 wa s morphologically normal. Heterozygous mice had decreased expression of KCN Q2 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.