A large-scale mutagenesis screen to identify seizure-resistant zebrafish

Epilepsia. 2007 Jun;48(6):1151-7. doi: 10.1111/j.1528-1167.2007.01075.x. Epub 2007 May 23.


Purpose: Zebrafish are a vertebrate organism ideally suited to mutagenesis screening strategies. Although a genetic basis for seizure susceptibility and epilepsy is well established, no efforts have been made to study seizure resistance. Here we describe a novel strategy to isolate seizure-resistant zebrafish mutants from a large-scale mutagenesis screen.

Methods: Seizures were induced with pentylenetetrazole (PTZ). Zebrafish were analyzed between 3 and 7 days postfertilization (dpf). Genome mutations were induced in founders by using N-ethyl-nitrosourea (ENU). Seizure behavior was monitored by using a high-speed camera and quantified by locomotion-tracking software. Electrographic activity was monitored by using a field-recording electrode placed in the optic tectum of agar-immobilized zebrafish.

Results: Short-term PTZ exposure elicited a burst-suppression seizure pattern in 3-dpf zebrafish and more complex activity consisting of interictal- and ictal-like discharges at 7 dpf. Prolonged exposure to PTZ induced status epilepticus-like seizure activity and fatality in wild-type zebrafish larvae. With a PTZ survival assay at 6-7 dpf, we identified six zebrafish mutants in a forward-genetic screen covering nearly 2,000 F(2) families. One mutant (s334) also was shown to exhibit reduced behavioral activity on short-term PTZ exposure and an inability to generate long-duration ictal-like discharge.

Conclusions: Zebrafish offers a powerful tool for the identification and study of a genetic basis for seizure resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Disease Models, Animal*
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing*
  • Larva / genetics
  • Larva / physiology
  • Locomotion / drug effects
  • Locomotion / genetics
  • Mutagenesis / genetics*
  • Pentylenetetrazole / pharmacology
  • Seizures / chemically induced
  • Seizures / epidemiology
  • Seizures / prevention & control*
  • Status Epilepticus / chemically induced
  • Status Epilepticus / prevention & control
  • Superior Colliculi / physiology
  • Zebrafish / genetics*


  • Pentylenetetrazole