Generation and analysis of zebrafish expressing KillerRed to induce oxidative stress in zebrafish models of amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disorder characterized by the muscle wasting, paralysis, hyperreflexia, and spasticity. Zebrafish has emerged as a powerful model to study various diseases, including ALS. Moreover, ALS transgenic zebrafish have been developed to study ALS. Oxidative stress has been hypothesis as a cause of neuron death in neurodegenerative diseases including ALS. However, the lack of experimental tools to target oxidative stress in specific cells has prevented direct evaluation of the hypothesis. We attempted to use a KillerRed, a genetically-encoded protein that generates reactive oxygen species (ROS) upon light activation, to induce oxidative stress in the zebrafish motor neurons and ubiquitously. We have shown its efficacy in live zebrafish and have applied KillerRed to stress motor neurons. Thus, we established a method to address the role of oxidative stress in an ALS model Zebrafish.