Fig. 1

Activation of the type I IFN response in nGD. a The 10 most significantly enriched GO terms for up-regulated genes illustrating enrichment of type I IFN-related pathways. The plot shows the enrichment p values. The number of differentially expressed genes out of the total number of genes included in the term detected by the array are indicated. n = 3, 14-day-old mice. b, c Gene set enrichment analysis (GSEA) of gene expression in Gba ^−/−compared to Gba ^+/– mice. b GSEA enrichment plot. False discovery rate (FDR) q value; normalized enrichment scores (NES). c Heat map displaying the relative expression level of proteins in the interferon signaling set, sorted by their fold change. Depicted are the top 51 genes. d qPCR analysis of Irf7 mRNA in the VPM/VPL obtained from 16-day-old mice and of Ifnb1 and Ifna2 mRNA in cortical tissues obtained from 21-day-old mice. **p < 0.001, *p < 0.005. Values are shown as fold change in mRNA levels (Gba ^−/− versus control) and are means ± s.e.m, n = 3–4. e ELISA analysis of IFNα and IFNβ protein levels in cerebral brain tissue obtained from 21-day-old control and Gba ^−/− mice. IFNα and IFNβ were not detected in control samples. *p < 0.005. Values are means ± s.e.m, n = 3 (upper panel). IFNβ protein levels in cerebellum of two human type 2 GD patients (n = 2) compared to age-matched control brains (n = 4). p value = 0.06 (lower panel)