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Updated: Oct 13, 2025
Preparation and Implantation of Electrodes for Electrically Kindling VGAT-Cre Mice to Generate a Model for Temporal Lobe Epilepsy
Published on: August 17, 2021
A novel LGI1 mutation causing autosomal dominant lateral temporal lobe epilepsy confirmed by a precise knock-in mouse
Ping Hu1, Dan Wu2,3, Yan-Yu Zang2,3
1Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health care Hospital, Nanjing, China.
Aims:
This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model.
Methods And Results:
A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G/D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G/+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G/D51G mice, and oxcarbazepine appeared to be the most effective.
Conclusions:
We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G/+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.
