Human Mutated MYOT and CRYAB Genes Cause a Myopathic Phenotype in Zebrafish

Myofibrillar myopathies (MFMs) are a group of hereditary neuromuscular disorders sharing common histological features, such as myofibrillar derangement, Z-disk disintegration, and the accumulation degradation products into protein aggregates. They caused by mutations in several genes that encode either structural proteins or molecular chaperones. Nevertheless, mechanisms which mutated result aggregation still unknown. To unveil role myotilin αB-crystallin pathogenesis MFM, we injected zebrafish fertilized eggs at one-cell stage with expression plasmids harboring cDNA sequences human wildtype MYOT (p.Ser95Ile) CRYAB (p.Gly154Ser). We evaluated effects on fish survival, motor behavior, muscle structure development. found transgenic showed morphological defects were more severe those overexpressing mutant genes. developed myopathic phenotype consistent myopathy, including formation Results indicate pathogenic associated MFM cause functional impairment skeletal zebrafish, thereby making this non-mammalian organism powerful model to dissect disease find possible druggable targets.