Fig. 2: Sex-focused examination of disease progression and motor symptomatology.

A Survival plot for M83 hemizygous mice. Percent survival of the mice plotted across the days post-injection (dpi) with the experimental endpoint being 130 dpi. Almost 30% of the male Hu-PFF-injected mice succumbed to their symptoms/disease progression a couple days prior to the 120 dpi time point. Group differences in survival rate were examined using general linear models, and a significant group by sex interaction was observed whereby male Hu-PFF-injected mice had lower survival rates (n = 84 mice; p = 0.000999). Of the mice that did not survive within the time frame examined (<130 dpi), the mice sustained motor symptomatology for on average 23 days. Shading represents a 95% confidence interval. B Percentage of mice showing motor symptoms across the number of days post-injection. No significant differences between the sexes were observed with regards to the percentage of mice being symptomatic (n = 84 mice). Shading represents a 95% confidence interval. C With regards to motor symptom onset, in terms of days post-injection, no significant differences were observed between the sexes (n = 84). The error bars indicate the data spread up to 1.5 times the interquartile range. D Weight trend across disease progression. Significant inverted U-shaped trajectory for Hu-PFF-injected mice, with weight loss as of 90 dpi (compared to PBS-injected mice) (n = 329 mice; p = 0.0056), regardless of sex. Shading represents ±1 standard error of the mean. E Average rotarod performance across time showed no significant differences between injection groups and sex (n = 256 mice). Shading represents ±1 standard error of the mean. F–I When interpreting the plot, the y-axis (Proportion Failed/Successful) shows the percentage of mice (or subjects) that failed to last more than 3 min on the wire hang test or successfully completed the pole test. The closer the line is to 100%, the more successful/unsuccessful the subjects were. The x-axis (Time in seconds) indicates the time taken to successfully complete the pole test/the amount of time they lasted on the wire under the 3-min successful cut-off. As time increases, the plot tracks the proportion of subjects who were successful/failed by that time. Next, the lines show the cumulative success/failure rates over time for the two injection groups. Shading represents a 95% confidence interval. F, G Wire-hang performance at 90 (left) and 120 (right) dpi. Significant difference in the proportion of mice that failed (<3 min) between injections groups (90 dpi: n = 186 mice; p = 0.0132; 120 dpi: n = 93 mice; p = 0.00032), with higher rates of failure for the Hu-PFF-injected mice (red dashed line); no sex difference observed. H, I Pole Test performance at 90 (left) and 120 (right) dpi. Hu-PFF-injected mice had lower proportions of mice successfully passing the test, and took significantly longer to descend the pole compared to their saline injected counterparts (90 dpi: n = 189 mice; p = 0.0304; 120 dpi: n = 87 mice; p = 0.017). See Supplementary Fig. 5 for visualization of non-significant injection groups by sex differences for the weight and rotarod analysis, and sex-specific injection group effects for the wire hang and pole test at 90 and 120 dpi. Purple color denotes PBS-injected mice and orange color denotes Hu-PFF injected mice. Line type was used to denote each of the sexes: solid line (with blue shading) for male and dashed line (with red shading) for female mice, except when no sex differences are displayed solid lines then denote both sexes grouped together. Data point shapes also denote the sex of the mice: triangle for males and round for females.