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. Author manuscript; available in PMC: 2013 Jun 21.
Published in final edited form as: Neuron. 2012 Jun 21;74(6):1031–1044. doi: 10.1016/j.neuron.2012.05.009

Figure 1. Sustained reduction in human and mouse huntingtin mRNA and protein by transient ASO infusion into the CNS.

Figure 1

(A) Dose response for HuASO in the brain of BACHD mice immediately following continuous two-week infusion of a human huntingtin targeting ASO (HuASO) at 10, 25 or 50 μg/day. Human huntingtin mRNA levels determined by qPCR and are expressed as mean ± SEM percent (%) of human huntingtin mRNA relative to saline treated controls (n=3 per dose).

(B–E) Animals treated with 50 μg/day HuASO euthanized at 0, 4, 8, 12 and 16 weeks post-treatment termination (n=4 per time point per dose). (B) Concentrations of accumulated HuASO in brain tissue measured by capillary gel electrophoresis. (C) Levels of human mRNAs as measured by qPCR. (D) Soluble mutant huntingtin levels quantified with time resolved forester resonance energy transfer (TR-FRET) assay. (E) Immunoblot of total huntingtin levels in brains of HuASO infused mice. The more slowly migrating band is human huntingtin protein (BACHD Tg); the more rapidly migrating band is endogenous mouse huntingtin (Mouse Htt).

(F–H) Animals treated with 75 μg/day MoHuASO euthanized at 0, 2, 4, 6, 8, 11 and 16 weeks post-treatment termination (n=4 per time point per dose). Levels of (F) human and mouse (G) huntingtin mRNAs as measured by qPCR. (H) Immunoblot of total huntingtin levels in brains of infused mice. Asterisks (*p<0.05, **p<0.01, and ***p<0.001) denote statistically significant changes relative to saline infused animals (Two-way ANOVA and Bonferroni’s post hoc tests). See also Figure S1.