Fig. 1
An adult-onset zebrafish model of SOD1-G93A amyotrophic lateral sclerosis. (A) The human ALS variant SOD1-G93A was ubiquitously overexpressed in zebrafish. Western blot for human and zebrafish SOD1 protein in lysates from adult skeletal muscle tissue. The membrane was Coomassie-stained to verify equal protein loading. See Supplementary Fig. 2 for full image of the blot. (B) Timeline of the phenotypic changes that occur in this adult-onset ALS model. In SOD1G93A zebrafish, early pathophysiological changes in the nervous system begin to develop at the neuromuscular junction at ~ 20 weeks of age. The disease progresses between 30–60 weeks of age, with loss of motor neurons and skeletal muscle atrophy being observed by 40 weeks of age. This sequential and gradual degeneration of the neuromuscular system is characteristic of human ALS. Brightfield images of Cresyl violet stained spinal cord tissue sections from (C,E) wildtype and (D,F) SOD1G93A zebrafish at the 40-week time point. Black bars = 50 µM. (G) Spinal cord motor neuron counts at the 20-week time point and 40-week time point in a 36 µm thick piece of spinal cord from wildtype and SOD1G93A zebrafish (n = 15–16). **** = p < 0.0001.
