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ZFIN ID: ZDB-PUB-191005-4
Targeted knockout of GABA receptor gamma 2 subunit provokes transient light-induced reflex seizures in zebrafish larvae
Liao, M., Kundap, U., Rosch, R.E., Burrows, D.R.W., Meyer, M.P., Bencheikh, B.O.A., Cossette, P., Samarut, É.
Date: 2019
Source: Disease models & mechanisms   12(11): (Journal)
Registered Authors: Meyer, Martin, Samarut, Eric
Keywords: Epilepsy, GABA, GABA receptor, Zebrafish
Microarrays: GEO:GSE134951
MeSH Terms:
  • Animals
  • Disease Models, Animal*
  • Gene Knockout Techniques
  • Larva
  • Light
  • Protein Subunits/physiology
  • Receptors, GABA-A/deficiency
  • Receptors, GABA-A/physiology*
  • Reflex/physiology
  • Seizures/etiology*
  • Transcriptome
  • Valproic Acid/therapeutic use
  • Zebrafish
PubMed: 31582559 Full text @ Dis. Model. Mech.
Epilepsy is the most common primary neurological disorder characterized by the chronic tendency of a patient to experience epileptic seizures, which are abnormal body movements or cognitive states that result from excessive, hypersynchronous brain activity. Epilepsy has been found to have numerous etiologies and whilst about two thirds of epilepsies were classically considered idiopathic, a majority of those is now believed to be of genetic origin. Mutations in genes involved in GABA-mediated inhibitory neurotransmission have been associated with a broad range of epilepsy syndromes. Mutations in the GABA-A receptor gamma 2 subunit gene (GABRG2), for example, have been associated with absence epilepsy and febrile seizures in humans. Several rodent models of GABRG2 loss-of-function depict clinical features of the disease, however, alternative genetic models more amenable for the study of ictogenesis and for high-throughput screening purposes are still needed. In this context, we generated a gabrg2 knock-out zebrafish model (R23X) that displayed light/dark-induced reflex seizures. Through high-resolution in vivo calcium imaging of the brain, we showed that this phenotype is associated with widespread increases in neuronal activity that can be effectively alleviated by the anti-epileptic drug valproic acid. Moreover these seizures only occur at the larval stages but disappear after one week of age. Interestingly, our whole transcriptome analysis showed that gabrg2-KO does not alter the expression of genes in the larval brain. As a result, gabrg2-/- zebrafish is a novel in vivo genetic model of early epilepsies that opens new doors to investigate ictogenesis and for further drug-screening assays.