Decreased viability and absence-like epilepsy in mice lacking or deficient in the GABA(A) receptor alpha 1 subunit

作者：Arain Fazal M; Boyd Kelli L; Gallagher Martin J^*

来源：Epilepsia, 2012, 53(8): E161-E165.

DOI：10.1111/j.1528-1167.2012.03596.x

• Generalized
• Inhibition
• Electroencephalogram
• Electromyography
• Ethosuximide

Autosomal dominant mutations S326fs328X and A322D in the GABA(A) receptor alpha 1 subunit are associated with human absence epilepsy and juvenile myoclonic epilepsy, respectively. Because these mutations substantially reduce alpha 1 subunit protein expression in vitro, it was hypothesized that they produce epilepsy by causing alpha 1 subunit haploinsufficiency. However, in a mixed background strain of mice, alpha 1 subunit deletion does not reduce viability or cause visually apparent seizures; the effects of alpha 1 subunit deletion on electroencephalography (EEG) waveforms were not investigated. Here, we determined the effects of alpha 1 subunit loss on viability, EEG spike-wave discharges and seizures in congenic C57BL/6J and DBA/2J mice. Deletion of alpha 1 subunit caused strain- and sex-dependent reductions in viability. Heterozygous mice experienced EEG discharges and absence-like seizures within both background strains, and exhibited a sex-dependent effect on the discharges and viability in the C57BL/6J strain. These findings suggest that alpha 1 subunit haploinsufficiency can produce epilepsy and may be a major mechanism by which the S326fs328X and A322D mutations cause these epilepsy syndromes.

• 出版日期2012-8