作者
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
发表日期
2009/3/31
期刊
Neurobiology of disease
卷号
33
期号
3
页码范围
499-508
出版商
Academic Press
简介
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 …
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