Phenotypic analysis of catastrophic childhood epilepsy genes

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. Local field potential recordings (LFP) were used to screen similar to 3300 larvae. 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. 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. Griffin et al used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing childhood epilepsies for which they evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Their study provides a useful resource for the future functional analysis and/or identification of potential anti-epileptic therapies.

Automated summary

Griffin et al used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing childhood epilepsies, for which they evaluated larval phenotypes using various analyses and created an open-source database, providing a valuable resource for the neuroscience community for future functional analysis and potential therapeutic identification.