Extended Data Fig. 9: In vivo examination of neuronal biomarker and CAG repeat gene regulation in treated WT and zQ175 het mice.
From: Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease
a, Timeline overview for the 1-month in vivo RT–qPCR study. Six-month-old WT or zQ175 het mice were treated with unilateral injections of AAV2/1+2 encoding either ΔDBD (n = 8 WT, n = 9 zQ175), ZFP-B (n = 6 WT, n = 9 zQ175) or ZFP-D (n = 6 WT, n = 8 zQ175) in the right hemisphere. PBS was injected into the left hemisphere. b,c, Normalized allele-specific transcript levels for Q175 (b) and WT (c) Htt. d–u, Normalized RT–qPCR levels for total Htt (d), 12 mouse genes with TSS-adjacent CAG repeats (e–p) and five neuronal biomarker transcripts (q–u). b–u, The ratio of the normalized transcript level for the AAV-treated hemisphere to that of the PBS-treated hemisphere is shown for each mouse in the WT (left panel) and zQ175 het (right panel) treatment groups. Mean ± s.d.; unpaired two-tailed t-test with Welch’s correction. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. e–p, The length of the closest CAG tract (≤ three mismatches per 6× CAG site; see Extended Data Fig. 8g) and its distance to the TSS are shown for the mouse and human ortholog of each profiled gene.
