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Research Discovery

Zebrafish enable large-scale analysis of catastrophic childhood epilepsy genes

By June 15, 2021July 2nd, 2021No Comments

Dozens of genes have been implicated in catastrophic childhood epilepsies — hard to treat forms of epilepsy characterized by persistent seizures. There have been few animal models available to study the effects of these genes, limiting our understanding of their roles in epilepsy and hampering the development of new drug treatments. But a new paper from Scott Baraban’s lab shows that zebrafish can be used to study many different genes involved in catastrophic childhood epilepsies, much more quickly than would be possible using mice.

Baraban is an adjunct professor of neuroscience at UC Berkeley’s Helen Wills Neuroscience Institute and a professor of neurological surgery at the UCSF Weill Institute for Neuroscience. The paper, published in Communications Biology, describes how his team used CRISPR-Cas9 gene editing to create 40 lines of zebrafish, each with a mutation in a single gene associated with catastrophic childhood epilepsy. Baraban’s team then extensively characterized these zebrafish lines, assessing their survival, behavior, and neural activity. They identified epileptic-like seizure activity in zebrafish lines for eight genes.

Three sets of black lines, roughly in the shape of circles, labeled respectively: low speed movement, high speed movement, and seizure-like movement. Low speed and high speed movement are both thin circles, and seizure-like movement is a thick circle.

Examples of larval zebrafish movement from the paper: Griffin, A. et al., Commun Biol 4, 680 (2021). https://creativecommons.org/licenses/by/4.0/

Detailed information on these genes, as well as the others tested, is publicly available on a website created by the Baraban lab, called the Epilepsy Zebrafish Project. Additionally, the lab will provide all of the zebrafish lines to other interested researchers, in the hopes that these new resources will advance understanding of catastrophic childhood epilepsy and facilitate the development of new treatments.

Read the paper: Phenotypic analysis of catastrophic childhood epilepsy genes by Griffin, A., Carpenter, C., Liu, J. et al., Communications Biology (June 2021)

By Rachel Henderson

Additional Information

Related new research: In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish by Liu, J., Salvati, K., and Baraban, S., iScience (May 2021)