Fig. 6: Upregulation of Clu-201 result in differential gene expression and isoform usage.

A A cluster dendrogram depicting the repertoire of Clu isoforms detected using targeted long-read sequencing in the rTg4510 cortex. Each row corresponds to a distinct isoform and each column represents a known exon. Colors refer to the presence of alternative splicing events (ES exon skipping, IR intron retention). B Visualization of the reference and selected novel isoforms of Clu characterized by exon skipping (ES), intron retention (IR), alternative promoters (AP) and novel cryptic exons (CE). Isoforms are coloured by structural category (pink – NIC, light pink – NNC). Shown in the final panel are the four DETs associated with tau pathology, and colors refer to transcripts shown in C. C Transcript expression of the four Clu DETs associated with tau pathology (see also Fig. 4). D Clu gene expression (normalized ONT full-length read counts) in WT (gray) and TG (black) mice across age. Isoform usage (proportion) of LR.Clu.139 stratified by (E) genotype and (F) age (n = 18). For the shown box-plot, the middle box represents the interquartile range (IQR), the middle line represents the median, and the whisker lines represent the minimum (quartile 1 – 1.5 × IQR) and the maximum (quartile 3 + 1.5 × IQR). DET differentially expressed transcript, FSM full splice match, ISM incomplete splice match, NIC novel in catalog, NNC novel not in catalog, WT wild-type mice, TG rTg4510 transgenic mice.