Phenotypic analysis of catastrophic childhood epilepsy genes: The Epilepsy Zebrafish Project

Griffin, A.; Carpenter, C.; Liu, J.; Grone, B.; Hamling, K.; Moog, M.; Dinday, M. T.; Figueroa, F.; Anvar, M.; Ononuju, C.; Qu, T.; Baraban, S. C.

doi:10.1101/2021.02.11.430844

bioRxiv · 10.1101/2021.02.11.430844

Phenotypic analysis of catastrophic childhood epilepsy genes: The Epilepsy Zebrafish Project

Griffin, A.·Carpenter, C.·Liu, J.·Grone, B.·Hamling, K.·Moog, M.·Dinday, M. T.·Figueroa, F.·Anvar, M.·Ononuju, C.·Qu, T.·Baraban, S. C.

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Abstract

Genetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes; ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADA and STXBP1. A unifying epilepsy classification scheme was developed based on local field potential recordings and blinded scoring from ~3300 larvae. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies.

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Griffin, A., Carpenter, C., Liu, J., Grone, B., Hamling, K., Moog, M., Dinday, M. T., Figueroa, F., Anvar, M., Ononuju, C., Qu, T., Baraban, S. C.. 2021-02-12. Phenotypic analysis of catastrophic childhood epilepsy genes: The Epilepsy Zebrafish Project. https://doi.org/10.1101/2021.02.11.430844

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