smc5 基因敲除斑马鱼肝脏转录组学分析.

Objective: To investigate the hepatic transcriptomic changes and the effects on metabolism of smc5 gene knockout zebrafish. Methods: The smc5 knockout zebrafish model was constructed by CRISPR/Cas9 technology and total RNA of the liver from wildtype and smc5-/- zebrafish was extracted for RNA sequencing, and gene expression profile of smc5-/- zebrafish was established. To better understand the differential expressed genes (DEGs) in the smc5-/-, DEGs were subjected to the Kyoto encyclopedia of genes (KEGG). q RT-PCR analysis was used to validated a set of genes. Results: The smc5 knockout lines of zebrafish carrying 2 base deletion were successfully constructed, which is expected to cause a frame shift. Further bioinformatic analysis revealed that p53 related pathways are significantly enriched among the genes upregulated. The downregulated DEGs were mainly enriched in glycolysis/gluconeogenesis, fatty acid degradation and metabolism, pyruvate metabolism. qRT-PCR results also validated that a set of genes of metabolism was downregulated. Conclusions: smc5 deficiency affects hepatic metabolism in zebrafish. The results of this study lay a foundation for further research on the potential mechanism of SMC5 gene in the regulation of glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]