TorsinB overexpression prevents striatal cholinergic interneuron degeneration and dystonic-like movements. (A) Growth curves of Cre control, Cre control;B-OE, Nes-SKI, and Nes-SKI;B-OE mice. Nes-SKI mice exhibited reduced postnatal growth, which was partially rescued by torsinB overexpression (two-way repeated measures ANOVA main effect of genotype F3, 26 = 60.65, p<0.0001, main effect of age F1.828, 47.53 = 794.8 p<0.0001, interaction F12, 104 = 9.831, p<0.0001; Cre control n = 7, Cre control;B-OE n = 8, Nes-SKI n = 7, Nes-SKI;B-OE n = 8). (B) Table of overtly abnormal postural and developmental phenotypes displayed by Nes-SKI and Nes-SKI;B-OE mice at P15. TorsinB overexpression reduces phenotypes that are prevalent in Nes-SKI mice (squinty eyes: Chi square test χ2 = 5.529, p=0.0187; twisted hindpaw: Chi square test χ2 = 6.234, p=0.0125). (C) Nissl staining of P10 brains from Cre control, Cre control;B-OE, Nes-SKI, and Nes-SKI;B-OE mice. TorsinB overexpression eliminates the morphological defects characteristic of Nes-SKI mice. (D) GFAP staining of P10 brains from Cre control, Cre control;B-OE, Nes-SKI, and Nes-SKI;B-OE mice. GFAP immunostaining illustrates the characteristic gliotic changes in Nes-SKI, including in cortex (arrows) and thalamus (circle). TorsinB overexpression eliminates gliotic changes in Nes-SKI mice.
Figure 4—source data 1. Information characterizing Nes-SKI;B-OE mice.