ER stress and UPR in the brain tissues of Hgsnat ^P304L mice. (A) A higher number of hippocampal genes with altered expression levels is found in Hgsnat^P304L than in Hgsnat-Geo mice. Venn diagram showing the number of genes that were upregulated or downregulated in hippocampal tissues of 4-mo-old Hgsnat^P304L and Hgsnat-Geo mice compared with the age- and sex-matched WT mice. Three mice (two male and one female) were studied for each genotype. (B–E) The expression levels of genes involved in lysosomal biogenesis (B), inflammatory response (C), and ER stress/UPR (E) show a trend for a greater increase, while the expression of genes involved in inhibitory synaptic transmission (D) show a trend for further decrease in Hgsnat^P304L compared with Hgsnat-Geo mice. (F and G) Normal protein levels the ER stress markers, CHOP and BiP, are detected in brain cortex tissues of 6-mo-old (F) and 8-mo-old (G) WT, Hgsnat^P304L, and Hgsnat-Geo mice by immunoblot. Graphs show band intensity values measured using ImageJ software. Individual results, means, and SD of experiments with three mice per genotype, per age are shown. P values were calculated using one-way ANOVA with Tukey post hoc test. Source data are available for this figure: SourceData FS2.