Absence epilepsy in apathetic, a spontaneous mutant mouse lacking the h channel subunit, HCN2

作者：Chung Wendy K; Shin Minyoung; Jaralmillo Thomas C; Leibel Rudolph L; LeDuc Charles A; Fischer Stuart G; Tzilianos Efthia; Gheith Ayman A; Lewis Alan S; Chetkovich Dane M^*

来源：Neurobiology of Disease, 2009, 33(3): 499-508.

DOI：10.1016/j.nbd.2008.12.004

• Hyperpolarization-activated cyclic nucleotide-gated channels
• Seizure
• Ethosuximide
• Ataxia
• HCN2
• HCN1
• HCN4
• Mouse chromosome 10
• Human chromosome 19p13.3

Analysis of naturally occurring mutations that cause seizures in rodents has advanced understanding of the molecular mechanisms underlying epilepsy. Abnormalities of I(h) and h channel expression have been found in many animal models of absence epilepsy. We characterized a novel spontaneous mutant mouse, apathetic (ap/ap), and identified the ap mutation as a 4 base pair insertion within the coding region of Hcn2, the gene encoding the h channel subunit 2 (HCN2). We demonstrated that Hcn2(ap) mRNA is reduced by 90% compared to wild type, and the predicted truncated HCN2(ap) protein is absent from the brain tissue of mice carrying the ap allele. ap/ap mice exhibited ataxia, generalized spike-wave absence seizures, and rare generalized tonic-clonic seizures. ap/+ mice had a normal gait, occasional absence seizures and an increased severity of chemoconvulsant-induced seizures. These findings help elucidate basic mechanisms of absence epilepsy and suggest HCN2 may be a target for therapeutic intervention.

• 出版日期2009-3
• 单位西北大学