Characterization of gene modifiers in a mouse model of epilepsy

Project: Research project

Project Details

Description

Dravet syndrome is a severe epilepsy with onset in infancy. Novel treatments are needed because many patients have seizures that cannot be controlled with available treatments. Mutations in the SCN1A gene cause Dravet syndrome by reducing the available voltage-gated sodium channels by approximately half of what is typically necessary for nervous system function. Interestingly, patients with the same SCN1A variant may differ in the severity of their symptoms suggesting that other genes, called modifier genes, influence the effects of SCN1A mutations. Similar to patients with Dravet syndrome, mice with only 50% of Scn1a expression have a severe epilepsy that resembles Dravet syndrome. Modifier genes also influence disease severity in the mouse model and we can use this system to identify the responsible genes. The goal of our study is to identify modifier genes that control differences in seizure severity and survival observed in Scn1a+/- mice. Our preliminary data have identified two microRNAs (miRNAs) as potential modifier genes. miRNAs act to regulate expression of other genes. We hypothesize that these miRNAs cause more seizures by further decreasing Scn1a expression below 50% expression. Therefore, blocking these miRNAs may improve seizure burden and survival, which may uncover a novel therapy for Dravet syndrome.
StatusActive
Effective start/end date7/1/206/30/21

Funding

  • American Epilepsy Society (Agmt 5/21/20)

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