Fig. 5: TRAP-Seq identifies age-dependent and brain region-specific gene alterations in GABAergic neurons of FXTAS.

a Schematic diagram for the TRAP experiment by using mouse brain tissues. Male mice were used for tissues dissection. b Volcano plots of gene expression changes in the GABAergic neurons from cortex and cerebellum of FMRpolyG+RNA; Gad2-Tagger mice compared to control mice. In the cortex, TRA-Seq was performed on 4 FMRpolyG+RNA; Gad2-Tagger mice and 4 controls at 3–4 months, and on 3 FMRpolyG+RNA; Gad2-Tagger mice and 3 controls at 6–7 months. In the cerebellum, TRA-Seq was performed on 2 FMRpolyG+RNA; CaMKIIα-Tagger mice and 3 controls at 3–4 months, and on 3 mice per genotype at 6–7 months. c, e Venn diagrams showing the number of hnRNPA2/B1 targets by eCLIP-Seq in cortex or cerebellum, and the overlapping targets with dysregulated genes in GABAergic neurons. Two-sided Fisher’s exact tests confirmed that these overlaps were highly significant at both stages and in both brain regions (Supplementary Data 6). Heatmap showing the fold change direction of the shared targets at two stages. d, f Dot plots of GO biological processes (P < 0.05) enriched in dysregulated mRNA targets of hnRNPA2/B1 by stages.