Figure 1

Genotype and miRNA profiling analysis from HD monkey brains and human miR-128a expression. A) Genomic DNA (gDNA) was isolated from the frontal cortex of 3 GFP control (C1-C3) and 8 HD monkeys (HD1-HD8). The gDNA was amplified using specific primers for mHTT and the PCR product was analyzed by gel electrophoresis. B) The fold change of HTT mRNA levels for the HD monkeys compared to the controls was quantitated by qPCR. C) Cluster diagram for dysregulated miRNAs in HD transgenic cortex. miRNA expression values (Log2 transformed & normalized microarray probe intensities) of the dysregulated microRNAs (P value < 0.05) in the HD and GFP control monkey cortex were median centered. Green squares represent lower than median levels of gene expression; black squares represent median levels of gene expression; red squares represent higher than median levels of gene expression. Legend units: 1.0 = differs from median probe intensity by one log 2 unit (2-fold). D) qPCR validation for the expression of 4 of the 5 miRNAs with significant Ingenuity analysis association to the HD pathway (miR-940 also showed association with the HD pathway, however, no Taqman assays were commercially available). T-test was used to determine significant differences between HD and control monkeys (P Value < 0.05 indicated by *). E) Expression of miR-128a was quantitated from control, pre-symptomatic (HD), and post-symptomatic (HD) human striatum samples. Total RNA was extracted and probed with specific Taqman primers to miR-128 for qPCR. T-tests were used to determine significant differences compared to the control group (P Value < 0.05 indicated by *).