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 |
| |
Institution: | 1. Division of Molecular Genetics and the Naomi Berrie Diabetes Center, Columbia University Medical College, Russell Berrie Medical Science Pavilion, Room 620, 1150 St. Nicholas Avenue, New York, NY 10032, USA;2. Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 10-201, Chicago, IL 60611-3008, USA;3. Department of Physiology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward Building 10-201, Chicago, IL 60611-3008, USA |
| |
Abstract: | Analysis of naturally occurring mutations that cause seizures in rodents has advanced understanding of the molecular mechanisms underlying epilepsy. Abnormalities of Ih 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 Hcn2ap mRNA is reduced by 90% compared to wild type, and the predicted truncated HCN2ap 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. |
| |
Keywords: | Hyperpolarization-activated cyclic nucleotide-gated channels Seizure Ethosuximide Ataxia HCN2 HCN1 HCN4 Mouse chromosome 10 Human chromosome 19p13 3 |
本文献已被 ScienceDirect 等数据库收录! |
|