Fig. 4

Lack of L-DL results in alternative splicing changes in the brain. a Diagram for the splicing reporter used to measure splicing efficiency. b Luciferase-WT or luciferase-Mut were introduced into control or L-DL KO N2a cells. Luciferase levels were plotted as fold differences of L-DL KO over controls (n = 3). c Number of significantly changed alternative splicing events in L-DL knockdown (KD) hippocampus. d Pie chart indicating the distribution of exon skipping, intron retention and other splicing events such as alternative 5′ splice site, alternative 3′ splice site and mutually exclusive exon in the hippocampus of L-DL KD mice. e Distribution of positive ΔPSI (PSI_{L-DL KD}-PSI_CTRL > 0) and negative ΔPSI (PSI_{L-DL KD}-PSI_CTRL < 0) for total changed splicing events (n = 2,181), exon skipping (n = 1,569), intron retention (n = 223) and other splicing events (n = 389) (P-value< 0.001). f Distribution of ΔPSI values (PSI_{L-DL KD}-PSI_CTRL) in splicing events such as exon skipping (n = 1,569), intron retention (n = 223) and other splicing events (n = 389) (P-value < 0.001). Data were shown as median within range. g-i Venn diagram demonstrating the intersections of genes with changed alternative splicing that identified in L-DL KD mouse brains and differentially expressed genes (DEGs) between aged and WT mouse brains (g), of genes with changed alternative splicing in L-DL KD mouse brains and DEGs between APP/PS1 and WT mice (h), of genes with changed alternative splicing in L-DL KD mouse brains and DEGs between AD patients and age-matched controls (i). Statistical analysis was performed using two-tailed Student’s t-test; ** P < 0.01; error bars denote SEM