Extended Data Fig. 6: mHTT–LC3 linker compounds lowered mHTT in vivo in mouse brains.
From: Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds
a, Western blots (4 mice (3 months old) for each group) and quantifications of mHTT and wtHTT in the cortices from HdhQ7/Q140-knock-in mice with intracerebroventricular injection of the indicated compounds (2 μl at 25 μM for each mouse) for 10 days at one dose per day. HTT was detected by western blot using the 2166 antibody, and the statistical analysis was performed by one-way ANOVA and post hoc Dunnett’s tests. F, degree of freedom and post hoc P values are indicated below each bar plot. b, Similar to a, except that the compounds were delivered to 5-month-old HdhQ7/Q140 mice by intraperitoneal injection (0.5 mg kg−1) for 14 days at one dose per day. c, Similar to b, but from striata of intraperitoneally injected mice. The mice were injected at 10 months old for 14 days at one dose per day. d, Left, representative dot blot results (from two technical replicates) of the protein lysates from b using the 4C9 antibody, which preferentially detects mHTT aggregates23. Middle, quantification of the dot blots based on the averaged signals from two technical replicates. Right, measurement of mHTT aggregates by the 4C9–4C9 HTRF assay23. In all panels, n indicates the number of mice tested, and bars represent mean and s.e.m. For quantification, two to three technical replicates were averaged for each mouse. Statistical analysis was performed by one-way ANOVA with post hoc Dunnett’s tests, and F, degree of freedom and post hoc P values are indicated in each bar plot.
