Figure 2. Differential amelioration of behavioral deficits and selective neurodegenerative pathology in BACHD mice with genetic mHTT reduction in cortical or striatal neurons.

A cohort of BACHD, BE, BR, BER, and WT littermate mice in FvB/NJ background were tested for longitudinal behavioral deficits. Two motor tests were used: Accelerating Rotarod at 6m (a) and 12m (b) of ages, and spontaneous locomotion in an Automated Open-Field Test at 6m (c) and 12m (d) of ages. Moreover, the mice were also tested for psychiatric-like behavioral deficits using two tests: depression-like behaviors in the Forced Swimming Test (e) and anxiety-like behaviors in the Light-Dark Box Exploration Test (f). Mice of different genotypes at 12m of age were used to quantify forebrain weights (g) in addition to unbiased stereological measurement of cortical (h) and striatal (i) volumes. One-way ANOVA followed by LSD post hoc test was applied for all behavioral studies. *P < 0.05, **P < 0.01, ***P < 0.001, values represent means ± SEM. For 6-month Rotarod and Open Field Tests, n = 14, 14, 15, 13 and 15 for WT, BACHD, BR, BE and BER, respectively; for all other behavioral tests, n = 12 per genotype; n = 8 per genotype in all pathological studies (more detailed statistics in Supplementary Table 1).