Fig. 4: ATXN2-Q33 causes motor deficits, NMJ changes and Purkinje cell degeneration in a mouse mutant TDP-43 background.

A, B Behavioral data presented using a generalized (non-)linear mixed model, corrected for sex, weight and longitudinal acquisition. A Accelerating rotarod analysis reveals reduced latency to fall in Q^33/+;TDP-43^Tg/+ mice as compared to Q^22/+;TDP-43^Tg/+ mice. B Q^33/+;TDP-43^Tg/+ mice show grip strength deficits as compared to NTg control and Q^22/+;TDP-43^Tg/+ mice. Curves reflect the mean and confidence interval bands correspond to 2x SD. Statistical significance is indicated by the gray areas. n ≥ 8 mice for each genotype and sex. See Supplementary Data 2 and 3 for details on N, SD and P value. C–G Quantification of lumbrical NMJs in 24-months-old Q^33/+;TDP-43^Tg/+and Q^22/+;TDP-43^Tg/+male mice. Individual panels show C NMJ number, D representative immunohistochemistry (IHC) images of NMJs with α-bungarotoxin (BTX), E NMJ area, F NMJ perimeter, and G overlap between pre- and post-synaptic parts of the synapse. All quantifications were performed with BTX (C, E, F) or BTX combined with SV2/2H3 IHC G. n = 3 mice for each genotype. Two-tailed unpaired t test (**P = 0.0044 (E, F)). Data are mean ± SD. D Scale bar is 10 µm. H Calbindin (CALB1) immunohistochemistry in the cerebellum. Inserts show Purkinje cells (PC) at higher magnification. Scale bar is 250/50 µm. I Quantification of PC density (midsagittal cerebellum sections, lobules VI–VIII) shows reduced PC density in Q^33/+;TDP-43^Tg/+ mice as compared to NTg controls. n = 7 mice for NTg, n = 8 for TDP-43^Tg/+, n = 4 for Q^22/+;TDP-43^Tg/+ and n = 9 for Q^33/+;TDP-43^Tg/+. NTg vs Q^33/+;TDP-43^Tg/+ *P = 0.019 (one-way ANOVA with Dunnett’s multiple comparison test). Data are mean ± SD. Source data are provided as a Source Data file for C, E–G, I.