Figure 5. N40K-Tg mice exhibit AD-related splicing defects enriched in synaptic function.

a, Age-dependent increase of mapped intronic reads and histogram of splicing deficiency score of individual transcripts in Tg mice (Tg396, 3-month-old: WT n = 3, and Tg n = 3, 12-month-old: WT n = 3, and Tg n = 3 biologically independent mouse samples). We quantified the percentage of intron reads (Student's t-test, two-tailed) and transcript splicing deficiency (Kolmogorov–Smirnov test). b, Increase of mapped intron reads and histograms of splicing deficiency scores of individual transcripts in ROS/MAP human AD cases²³ (Ctrl n = 18, AD n = 35, left: Student's t-test, two-tailed; right: Kolmogorov–Smirnov test). Each point represents data of individual human cases c, Venn diagram of mouse and human splicing-defective transcripts. d, Pathway enrichment analysis of shared splicing-defective transcripts in the Tg and AD, showing selected pathways from Supplementary Table 12. FDR was derived from p values (Fisher's exact test) by the BH procedure. e, Four examples of enriched PPI modules (Supplementary Table 13), with the proteins in iPSD highlighted in red. Each dot represents a protein, whereas the interaction is indicated by connected lines. f, Validation of intron retention in selected transcripts by the density of RNA reads (ex: exon; in: intron) and RT-PCR. Red boxes show genomic regions selected for quantifying RNA-seq reads (Student's t-test, two-tailed). Scale bar, 10 kb. g, qRT-PCR analysis of Gabra2 transcripts (Student's t-test). Data are shown as mean ± SEM. in a, f, g. each point represents a data point of one mouse (WT n = 3, and Tg n = 3). Full statistical information is in Source Data Statistics.