In vivo modeling of epileptic encephalopathies caused by mutations in aminoacyl-tRNA synthetases in zebrafish.

Epileptic encephalopathies (EE) are serious chronic neurological disorders hallmarked by early onset and refractory seizures. They are usually caused by genetic factors, although in most cases the causative genes are unknown. Therefore there is a growing need for novel neurodevelopmental vertebrate models. Zebrafish has emerged as a promising model organism for the study of a variety of central nervous system disorders including epilepsy because of their rich behavioral repertoire that is amenable to both genetic and pharmacological manipulation. Thus, we aim in this research project is to generate and characterize novel in vivo zebrafish models for human EE caused by mutations in aminoacyl-tRNA synthesases (ARS). We will model a deficiency of these novel genes implicated in EE in zebrafish using genome editing tools and look for evidence of an epilepsy phenotype based on genetic and electrophysiological methods. Our goal is to attain new insights into the etiology of ARS-induced EE. This in vivo functional validation will help us to understand the pathophysiology of EE, and additionally will form a starting point for future pharmacological studies, which may uncover potential therapeutic strategies for improved seizure control that could be utilized for the discovery and development of new antiepileptic drugs with novel mechanisms of action.

Keywords:NEUROSCIENCE

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing

Project type:Collaboration project