Zebrafish (Danio rerio) is emerging as a promising model in the study of the central nervous system, and more and more studies show the suitability of this model to study a number of neurodegenerative diseases. Approximately 75% of patients with Dravet syndrome have mutations in the SCN1A gene, which encodes the α subunit of type I sodium channel. The orthologue of this gene in the zebrafish is named scn1Lab and shares 77% identity with the human gene. There is a mutant zebrafish model with a mutation in the scn1Lab gene called the didy mutant. Didy embryos develop spontaneous seizures from 3 days post fertilization (dpf), do not survive beyond 14 dpf and have a darker pigmentation.

The main aim of this project is to set up a new efficacy assay in Dravet syndrome using didy mutants. In the first place, the didy line was acquired through an MTA (material transfer agreement) and once the fish reached adulthood, the heterozygote individuals were identified to establish the line. In each clutch, the 25% of the embryos are homozygote mutant. First, the mutants were identified based on their dark pigmentation and they were genotyped to confirm they carried the mutation. Currently, we are characterizing the didy mutants based on their locomotor activity, because it has been described that they show an increase in movement velocity due to the spontaneous seizures they present. Finally, we will test 3-4 reference products described in the literature that correct these altered behaviours to validate the assay. In this way, we will establish a new screening assay to test potential compounds with therapeutic effect in Dravet syndrome.