Modulation of insulin secretion through RBFOX2-mediated alternative splicing [RNA-seq Mouse Iselt]

Recent studies have identified dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing in the onset of diseases including diabetes. Here we investigated the role of RBFOX2 in the pancreatic β cell through the conditional mutation of Rbfox2 in the mouse pancreas (Pdx1:Cre; Rbfox2fl/lf) and RNAi experiments in the mouse insulinoma cell line, MIN6. We then identified the direct targets of RBFOX2 in the mouse β cell transcriptome my eCLIP-Seq in MIN6 cells. To investigate alternative splicing sensitive genes in the presence and absence of RBFOX2, we generated Rbfox2 conditional mutant mice by combining a single Pdx1:CRE allele (B6.FVB-Tg(Pdx1-cre)6Tuv) (Hingorani et al., 2003) with one or two Rbfox2flox/flox alleles (B6.129S2-Rbfox2tm1.1Dblk/J) (Gehman et al., 2012). We then performed gene expression profiling analysis using data obtained from RNA-seq. Three biological replicates for each genotype. Comparative gene expression profiling analysis of RNA-seq data form non-cre control islets and Rbfox2-mutant islets.