Referenced in: none

Automatically associated channels: HCN2

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

Authors: Wendy K Chung, Minyoung Shin, Thomas C Jaramillo, Rudolph L Leibel, Charles A LeDuc, Stuart G Fischer, Efthia Tzilianos, Ayman A Gheith, Alan S Lewis, Dane M Chetkovich

Journal, date & volume: Neurobiol. Dis., 2009 Mar , 33, 499-508

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19150498

Abstract
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.