Figure 8.

Suppression of ataxin-7-92Q transgene expression in SCA7 mice after symptom onset prevents further aggregate pathology. (A) We immunostained sagittal cerebellar sections for ataxin-7 (red), calbindin (green) and 4′,6-diamidino-2-phenylindole (DAPI) (blue), and as shown here, could readily detect PCs with ataxin-7-positive aggregates. Scale bar, 25 µm. (B) To quantify ataxin-7 aggregate burden, we counted the number of PCs with ataxin-7-positive nuclear inclusions, and divided by the total number of PCs present in the section (n = 3–8 mice/group). PrP-floxed-SCA7-92Q BAC mice accumulate ataxin-7 aggregates beginning at 10 weeks of age, and by 43 weeks of age, ∼50% of PCs display aggregates. Note that only ∼23% of PCs from 43-week-old tamoxifen-treated bigenic animals, however, exhibit ataxin-7 aggregates, which is a significant reduction in comparison to age- and littermate-matched tamoxifen-treated SCA7 singly transgenic mice or oil-treated bigenic mice (P < 0.05, one-way ANOVA with Bonferonni post-test). Error bars = SEM.