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. 2024 Feb 22;147(5):1784–1798. doi: 10.1093/brain/awae063

Figure 5.

Figure 5

Transcriptional dysregulation in the striatum of zQ175 mice is not alleviated by loss of Msh3 expression. (A–D) Volcano plots illustrating gene expression changes between (A) zQ175 and wild-type mice (B) zQ175:Msh3−/− and wild-type mice, (C) zQ175 and zQ175:Msh3−/− mice and (D) Msh3−/− and wild-type mice, at 6 months of age. (E) Of the 2486 genes dysregulated in zQ175 mice as compared to wild-type mice at 6 months of age, 2408 showed negligible reversal, with a total of 15 genes showing full reversal and 51 partial reversal, indicating that only 3% of genes were rescued, a level considered to be background. Of the known 266 genes dysregulated in striatal tissues across models, 258 were detected as dysregulated, with none reversed and one exacerbated. (F and G) Expression levels for (F) striatal genes of interest: Cnr1, Drd1, Pde10a, Penk and Ppp1r1b and (G) the DNA mismatch repair genes Msh3, Msh2, Msh6 plotted as variance stabilizing transformed counts derived using DESeq2. Box and whisker plots represent median and 25th and 75th percentiles with bars drawn from minimum to maximum. They show there was no change in expression due to loss of Msh3. n = 8/genotype, four males/four females for each genotype except zQ175:Msh3−/− at five males/three females. HD = Huntington’s disease; WT = wild-type.