Epilepsy is a neurological disorder characterized by recurrent seizures or convulsions, which are caused by abnormal electrical activity in the brain. Seizures can vary in severity, duration, and frequency, and may involve convulsions, loss of consciousness, or sensory disturbances. According to the Epilepsy Foundation, epilepsy is the fourth most common neurological disorder and affects people of all ages, although it is more common in children and older adults.
Zebrafish have become an increasingly popular model organism for studying epilepsy because they share many similarities with human brain development and function, and many of the same genes that are associated with epilepsy in humans.
Zebrafish as a model organism for epilepsy research has the potential to help researchers better understand the underlying mechanisms of epilepsy, and to develop new treatments and therapies for this complex neurological disorder.
Compound testing using a chemical model or genetically modified zebrafish model.
Study patient genetic variants using genetically modified zebrafish models.
We use the zebrafish as an in vivo model to measure the functional effects of patient-derived genetic variation. In this way, human genetic variants identified in the clinic are quantitatively and qualitatively connected to model animal phenotypes.
Illustration of a successful precise point mutation of stxbp 1a in zebrafish. stxbp1a is a highly conserved zebrafish ortholog of human STXBP1 (87% identity). Using CRISPR/Cas9 technology, we were able to precisely generate a benign patient mutation at the conserved amino acid residue (CCC>CTG, p.P94L).
Modeling STXBP1 Patient Variants In Zebrafish. Precision genome editing targeting stxbp1 – a zebrafish ortholog of human the gene syntaxin-binding protein 1 (STXBP1) was used to generate two precise knock-in models of patient variants to assess differences in phenotypes in comparison to the established loss of function mutants. Download the poster.
Loss of function results in reduced swimming activity phenotype. Homozygous stxbp1a S42P mutants partially reproduce published stxbp1a loss of function movement phenotype, as suggested by single larval recordings in a 96-well plate locomotion assay where homozygous S42P mutant larvae trend towards reduced activity in baseline and PTZ-treated conditions (right panel; PTZ = pentylenetetrazole). Download the poster.
Age-matched animals from at least two different groups are compared. The animals are recorded in response to stimuli such as light/dark cycling and vibration. The software identifies and tracks animals to quantify many aspects of behavior, including:
The DanioVision software tracks the behavior of individual zebrafish larvae over time as they explore an arena.