PUBLICATION

Phenotypic analysis of catastrophic childhood epilepsy genes

Authors
Griffin, A., Carpenter, C., Liu, J., Paterno, R., Grone, B., Hamling, K., Moog, M., Dinday, M.T., Figueroa, F., Anvar, M., Ononuju, C., Qu, T., Baraban, S.C.
ID
ZDB-PUB-210605-3
Date
2021
Source
Communications biology   4: 680 (Journal)
Registered Authors
Baraban, Scott
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Child
  • Disease Models, Animal*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism*
  • Epilepsy/genetics*
  • Epilepsy/pathology
  • Epilepsy/physiopathology
  • Exome Sequencing/methods
  • Gene Expression
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Humans
  • Larva/genetics
  • Mutation
  • Phenotype
  • Survival Analysis
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
PubMed
34083748 Full text @ Commun Biol
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. Local field potential recordings (LFP) were used to screen ∼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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping