-Null Zebrafish as a Model for Studying -Associated Heart Malformation in Bosley-Salih-Alorainy Syndrome.

Mutations in can lead to diseases such as Bosley-Salih-Alorainy syndrome, involving severe cardiovascular malformations. However, the role of in cardiac morphogenesis remains unclear. is a homologous gene to human in zebrafish. We used CRISPR to make -null zebrafish that exhibited multiple heart malformations. In situ hybridization and sections revealed the morphological changes in mutants: enlarged ventricle with thickened myocardium and increased trabeculae, intensified OFT and inadequate heart looping, with electrocardiography supporting these pathological changes. High-speed photography captured cardiac pumping and revealed a significant decrease in cardiac output. Furthermore, lacking led to posterior body abnormality that affected movement ability, corresponding with the motor development delay in patients. Upregulation of paralogues in -null fish implied a compensatory mechanism between genes. Accordingly, we successfully constructed a -null model with a cardiac disease pattern which occurred in human -associated heart malformation. The study of in zebrafish can further promote the understanding of genes and related diseases.