A hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and its discovery has revolutionized our understanding of this devastating disease. Model systems are a valuable tool for studying ALS pathobiology and potential therapies. The zebrafish (Danio rerio) has particularly become a useful model organism to study neurological diseases, including ALS, due to high genetic and physiological homology to mammals, and sensitivity to various genetic and pharmacological manipulations. In this review we summarize the zebrafish models that have been used to study the pathology of C9orf72-related ALS. We discuss their value in providing mechanistic insights and their potential use for drug discovery.
Keywords: ALS; C9orf72; motoneuron; zebrafish.