Extended Data Fig. 6: zQ175 bridging data for ZFP-D and control treatments.
From: Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease
a,b, mRNA (a) or soluble protein (b) levels of WT and mHTT in zQ175 het neurons 10 d after infection with AAV2/1 + 2 ZFP-D as assessed by RT–qPCR (a), Singulex (mouse HTT) or MSD (mHTT) (b). LOD, limit of detection; Bkg, background limit. n = 3 biologically independent samples; mean ± s.d.; one-way ANOVA with Tukey’s multiple comparison test; mean ± s.d.; **** P < 0.0001. c,d, Quantitation of perinuclear (c) or nuclear inclusions (d) in ZFP+ NEUN+ cells for 2–6- (left) or 6–12- (right) month-old cohorts of zQ175 het mice treated with AAV2/1 + 2 ΔDBD or ZFP-D. BLOQ, below limit of quantitation. n = 4 mice; mean ± s.d.; two-tailed unpaired t-test with Welch’s correction; * P < 0.05, ** P < 0.01. e–g, Representative striatal immunostaining images from 2–4- (e) or 6–10- (f,g) month-old zQ175 het cohorts injected with AAV2/1 + 2 GFP (e,f) or ΔDBD.T2A.GFP (g); scale bar, 200 μm. HTT inclusions (mEM48), yellow; GFP, green; DARPP32, red; DAPI, blue. Expanded GFP+ and GFP– regions are shown at right; scale bar, 20 μm. Similar results were replicated in at least one independent experiment. h, Representative striatal GFAP and IBA1 immunostaining images from 6–10-month-old zQ175 het cohorts injected with AAV2/1 + 2 GFP; scale bar, 200 μm. GFP, green; DAPI, blue; GFAP, red; IBA1, yellow. Expanded GFP+ and GFP– regions are shown at right; scale bar, 50 μm. Similar results were replicated in at least one independent experiment. i–n, Quantitation of IBA1+ cells (i,l), GFAP+ cells (j,m) and GFAP intensity (k,n) in WT (left panels) or zQ175 (right panels) striata injected with AAV2/1 + 2 ΔDBD or ZFP-D for 2–6- (i–k) or 6–12- (l–n) month cohorts. n = 4 mice; mean ± s.d.; two-tailed unpaired t-test with Welch’s correction.
