【Animal modeling】-Effect of Fkbp51 knockout on alternative splicing of mouse liver transcriptome

  Objective: To study the effect of Fkbp51 knockout on gene alternative splicing in liver tissue by analyzing the expression profiles of Fkbp51 gene knockout and wild-type mice livers.

  Methods: The expression profiles of Fkbp51KO and WT mouse livers were sequenced by next-generation sequencing, and the alternative splicing analysis of RNA sequencing results was performed by TopHat to screen out the differences in intron retention (intron retetion, WT) in liver tissues of KO and WT mice. RI) and exon skipping (SE). These differentially alternative spliceosomes were subjected to gene ontology (GO) and metabolic pathway (kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis by the online tool DAVID, and these genes were annotated with the NCBI gene database.

  Results: (1) Deletion of Fkbp51 resulted in changes in mRNA alternative splicing in mouse liver; (2) Fkbp51 knockout resulted in changes in expression of alternative splicing in mouse liver mRNA; (3) Through GO and KEGG analysis, we found that These differentially alternatively spliced genes are mainly related to the metabolism, immunity, bile acid secretion and other pathways of fat-related derivatives. (4) Genes related to differential intron retention were mainly related to actin cytoskeleton regulation, and metabolism of amino acids and their derivatives.

  Conclusion: Fkbp51 gene knockout can alter the alternative splicing of mRNA in the genome, thereby affecting the metabolic function of mouse liver.