Characterization of seizures in a new mouse model of KCNT1 G288S

Awardee: Jill Silverman

Institution: UC Davis

Grant Amount: $68,667

Funding Period: February 1, 2025 - January 31, 2026

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Summary:

KCNT1-related epilepsy is an autosomal dominant NDD, resulting from de novo pathogenic variants in the sodium activated potassium channel, and are associated with Epilepsy of Infancy with Migrating Focal Seizures (EIMFS), and Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE), characterized by clusters of nocturnal motor seizures. Few animal models exist that carry any of the 64 known human variants described, to date. To that end, we will focus our proposed studies on a novel mouse model of the human gene variant G288S (corresponding to mouse Kcnt1 G269S), a mutation located within the sequence coding for the channel pore. This mouse model has substantial translational potential because we will investigate the impact of early life seizure on occurrence, recurrence, and severity of seizure phenotypes across the lifespan to aged adults, and severity and neuro and respiratory physiological phenotypes.