Back to Top
Charles H. Hood Foundation | Annapurna Poduri, M.D. – July 2016
By identifying innovative pediatric advancements and providing funding in the critical phases of development, we are able to expedite high-impact breakthroughs that improve the health and lives of millions.
portfolio_page-template-default,single,single-portfolio_page,postid-16653,ajax_fade,page_not_loaded,,no_animation_on_touch,qode-title-hidden,qode-child-theme-ver-1.0.0,qode-theme-ver-10.0,wpb-js-composer js-comp-ver-4.12,vc_responsive

Annapurna Poduri, M.D.

Assistant Professor in Neurology

Boston Children’s Hospital

Zebrafish Models of PCDH19-related Pediatric Epilepsy


Key Words: Epilepsy, Genetics, Zebrafish, Animal Models, Drug Screens, PCDH19

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.


Our goal is to establish genetic models of PCDH19-related epilepsy in zebrafish to study the cellular and network abnormalities underlying PCDH19-related epilepsy. Using the CRISPR/Cas9 system, we will introduce patients’ PCDH19 into this model system to evaluate for spontaneous seizures and proconvulsant-induced seizures that can be detected visually and with locomotion detection. In addition, we will perform electrophysiological recording to assess for tendency to seizures and to confirm that a given model is ‘epileptogenic.’ We then expose these models to anti-seizure medications to evaluate for reduction in seizures. These studies will set the stage for high-throughput drug screens of additional compound libraries, thus moving us toward the goal of “precision medicine” for this and other pediatric epilepsies.