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Published on: July 14, 2014
A large-scale mutagenesis screen to identify seizure-resistant zebrafish
Scott C Baraban1, Matthew T Dinday, Peter A Castro
1Epilepsy Research Laboratory in the Department of Neurological Surgery, University of California, San Francisco, California 94143, USA. scott.baraban@ucsf.edu
Epilepsia
|May 25, 2007
Summary
Researchers identified novel seizure-resistant zebrafish mutants using a large-scale mutagenesis screen. This study establishes zebrafish as a powerful model for investigating the genetic basis of seizure resistance.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Epilepsy and seizure susceptibility have a known genetic basis.
- Seizure resistance has not been extensively studied genetically.
- Zebrafish are suitable for large-scale mutagenesis screens.
Purpose of the Study:
- To develop a novel strategy for isolating seizure-resistant zebrafish mutants.
- To initiate a large-scale forward-genetic screen for seizure resistance.
Main Methods:
- Mutagenesis was induced using N-ethyl-nitrosourea (ENU) in zebrafish founders.
- Seizures were induced with pentylenetetrazole (PTZ) in 3-7 day postfertilization (dpf) larvae.
- Behavioral and electrographic seizure activity were quantified using high-speed cameras and electrophysiology.
Main Results:
- PTZ induced seizure patterns ranging from burst-suppression to status epilepticus in wild-type larvae.
- A PTZ survival assay identified six seizure-resistant mutants from nearly 2,000 F(2) families.
- One mutant (s334) showed reduced activity and impaired ictal-like discharge generation.
Conclusions:
- Zebrafish are a powerful model for studying seizure resistance.
- This screen identified novel genetic factors contributing to seizure resistance.
- Further studies can elucidate the mechanisms underlying genetic seizure resistance.
