Author(s): Ashton Gardner, Corbin Arnold
Mentor(s): Hung-Yu Shih, Yu-Chien Liu
Institution UTech
Wolfram Syndrome 2 (WS2) is a rare neurodegenerative disorder affecting multiple organs, including the nervous system. The disease is caused by mutations in the cisd2 gene, although the mechanisms by which cisd2 dysfunction leads to WS2 remain unclear. This research aims to validate an established zebrafish model of WS2 in our lab, elucidate underlying pathophysiological mechanisms, and facilitate compound screening for potential treatments. Using the CRISPR/Cas9 technique, we have knocked out the cisd2 gene and have validated key clinical features of Wolfram Syndrome 2, including optic nerve atrophy, hearing loss, juvenile-onset diabetes mellitus, and neurodegeneration. To investigate the impacts of Cisd2 defect on the nervous system, we will analyze the neural markers by in situ hybridization and qPCR analysis. Moreover, we will examine cellular proliferation and death by immunostaining and TUNEL assays. The results will reveal the function of Cisd2 in the nervous system and have a broad application to WS2 pathogenesis. This zebrafish model of WS2 offers a valuable platform to explore the underlying pathophysiological mechanisms and serves as a promising model for high-throughput drug screening.