HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model (original) (raw)
Figure 4
Effect of HDACI 106 on global gene expression profiles in the brain, cerebellum and heart of KIKI mice.
(A) 670 probes (655 unique genes) in total were affected by drug treatment in either tissue in either strain. A few drug-responsive genes were shared between the two strains. Quantification of the number of genes (among the 615 KIKI-related) that go in opposite direction after drug treatment show that 70–85% genes change but only in KIKI samples. In a subset of genes (mostly in cerebellum) this difference was statistically significant at P<0.005. (B) Heatmaps representing the gene expression profiling before and after treatment with 106 in brain (left), cerebellum (center) and heart (right) of KIKI mice (four replicates per condition). Fold changes of the genes differentially expressed in KIKI vs. WT (brain = 61, cerebellum = 318, and heart = 182 genes at P<0.005) are depicted before treatment (KIKI vs. WT, grey bars on the top) and after treatment (KIKI treated vs. KIKI untreated, blue bars on the top). Shades of red represent upregulation, shades of green downregulation. Genes and samples are clustered by similarity. (C) Most genes (67% in brain, 84% in cerebellum, 67% in heart) show coordinate changes towards normal levels after treatment. In a subset of these genes (34% in brain, 23% in cerebellum, 60% in heart) these changes reach statistical significance.