Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.
LGI1 in humans is responsible for a predisposition to autosomal dominant partial epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1 mutations cause epilepsy remain unclear. We have used a mouse chromosome engineering strategy to create a null mutation for the gene ortholog encoding LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities from routine histopathological analysis. After 12-18 days of age, the homozygous mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and running and die shortly thereafter. The heterozygous mutant mice do not develop seizures. Electrophysiological analysis demonstrates an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This mouse model, therefore, provides novel insights into the mechanism behind ADPEAF and offers a new opportunity to study the mechanism behind the role of LGI1 in susceptibility to myoclonic seizures.
MCG Cancer Center, School of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
Y Eugene
YE
Yu
Lei
L
Wen
Jeane
J
Silva
Zhongyou
Z
Li
Karen
K
Head
Khalid
K
Sossey-Alaoui
Annie
A
Pao
Lin
L
Mei
John K
JK
Cowell
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004594:Electrophysiology; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C492120:Lgi1 protein, mouse; D011506:Proteins; D018698:Glutamic Acid