Loss of αB-crystallin function in zebrafish reveals critical roles in the development of the lens and stress resistance of the heart.

摘要: Genetic mutations in the human small heat shock protein αB-crystallin have been implicated autosomal cataracts and skeletal myopathies, including heart muscle diseases (cardiomyopathy). Although these lead to modulation of their chaperone activity vitro, vivo functions maintenance both lens transparency integrity remain unclear. This lack information has hindered a mechanistic understanding diseases. To better define functional roles αB-crystallin, we generated loss-of-function zebrafish mutant lines by utilizing CRISPR/Cas9 system specifically disrupt two genes, αBa αBb We observed abnormalities penetrance phenotype was higher than mutants. finding is contrast with previously reported knock-out mice suggests that elevated orthologs critical for development. Besides its key role lens, uncovered another providing stress tolerance heart. The mutants exhibited hypersusceptibility develop pericardial edema when challenged crowding or exposed cortisol stress, which activate glucocorticoid receptor signaling. Our work illuminates involvement presumably through proteostasis network reinforces transparency.