Fig. 4.

Reduction of NeuN expression in the striatum by Hap1 depletion is dependent on the presence of mutant HTT. (A) Immunostaining of the brains of HD KI/Cas9 (KI/Cas9) and WT/Cas9 (Cas9) showing that AAV-Hap1 gRNA injection reduced NeuN staining only in the striatum of KI/Cas9 mouse brain. (B) Double-immunostaining of the striatum verified the transduction of AAV (red) and obviously reduced NeuN staining (green) in the AAV-Hap1 gRNA-injected striatum in a KI/Cas9 mouse as compared with a WT/Cas9 mouse. (C) Immunostaining also shows a decrease in DARPP-32 staining in the KI/Cas9 striatum by AAV-Hap1 gRNA injection. (D) Quantification of the number of NeuN-positive (from B) and DARPP-32–positive cells (from C) in the AAV-Hap1 gRNA-injected striatum of WT/Cas9 and KI/Cas9 mice, and in the AAV-control gRNA-injected striatum of KI/Cas9 mice. The data were obtained by counting 20 images from five animals per group. ***P < 0.001. (Scale bars, 15 μm [B]; 10 μm [C].)