Zebrafish Models of PCDH19-Related Pediatric Epilepsy

Epilepsy affects one in 200 children, many with a genetic etiology. Inherited and de novo heterozygous mutations in the X-linked PCDH19 gene are associated with “female-limited epilepsy,” characterized by refractory early onset seizures, intellectual disability, autism, and behavioral problems. To date, there are no PCDH19-specific treatments or animal models to study this condition.

Zebrafish have emerged as a simple, robust vertebrate model to study epilepsy and other neurodevelopmental diseases. Our preliminary data indicate that genome-edited zebrafish models of PCDH19-related epilepsy display behavioral and electrophysiological abnormalities. The focused goals of this proposal are to establish clinically relevant pcdh19 zebrafish models and to screen the effects of available AEDs.