Fig. 2

FTD/ALS-linked CHCHD10 mutants drive both CHCHD10 and TDP-43 pathogenesis in the CNS. a Representative images of brain sections from 10-month-old WT, CHCHD10^WT, CHCHD10^R15L, and CHCHD10^S59L mice immunostained for CHCHD10 in the frontal cortex. White boxes magnified in bottom panels. b Quantification of the percentage of soma in frontal cortex from Fig. (2a) with aggregated CHCHD10 (1-way ANOVA, F(2, 104) = 101.9, P < 0.0001: posthoc Tukey, ##p < 0.0001, n = 34–37 images/genotype from 4 mice/genotype). c Representative images of brain sections from 10-month-old CHCHD10^WT, CHCHD10^R15L, and CHCHD10^S59L mice immunostained for pS409/410-TDP-43 (green) and DAPI (blue). White boxes magnified in bottom panels. d Quantification of pS409/410-TDP-43 inclusions from Fig. (2c) (1-way ANOVA, F(2, 67) = 11.52, P < 0.0001: posthoc Tukey, #p < 0.005, n = 23–24 images/genotype from 4 mice/genotype). e Quantification of Flag-CHCHD10 colocalization with pS409/410-TDP-43 from Fig. (2c) (1-way ANOVA, F(2, 66) = 56.56, P < 0.0001: posthoc Tukey, ##p < 0.0001, n = 23 images/genotype from 4 mice/genotype). f RIPA-insoluble fraction the cortex of 10-month-old CHCHD10^WT, CHCHD10^R15L, and CHCHD10^S59L immunoblotted for TDP-43 and actin. g Quantification of the insoluble TDP-43 normalized to actin from Fig. (2f) (1-way ANOVA, F(2, 6) = 17.13, P = 0.0033: posthoc Tukey, *p < 0.05, **p < 0.01, n = 3 mice/genotype)