Lgi1-null mouse: a model for epilepsy

LGI1 (leucine-rich, glioma-inactivated 1) mutations are responsible for an inherited focal epileptic syndrome with onset in adolescence. LGI1-related epilepsy mutations result from a loss of function. We have used a strategy of conditional knockout to model the haploinsufficiency observed in the human genetic condition. According to Mendelian ratios, we have obtained LGI1+/- and LGI1-/- mice which are undistinguishable from wild type littermates at birth. At age P10, LGI1-/- mice start to have spontaneous frequent seizures monitored by EEG-video. The complete loss of LGI1 leads to premature death in the null-mutant mice around P15-P18 apparently from seizures. Morphological modifications (mossy fiber sprouting, gliosis, neuronal loss) subsequent to seizures are observed in the hippocampus of the LGI1-/- mice.

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Interest / Relevance: We have engineered the first LGI1-null mice which represent a novel genetic rodent model of focal-onset epilepsy with a 100 % prevalence of spontaneous seizures and age-dependant onset, comparable to the human syndrome. This epileptic mouse model may help develop therapeutic strategies to improve seizure control and developmental outcome and guide us towards novel therapeutic targets functionally different from the ion channels targeted by most anti-epileptic drugs.

Publications:

Unpublished

Reference:

RT00390