Fig. 1
Life span, disease duration, and end-stage αS lesions of different αS TG mouse lines. (a) Kaplan-Meier curves for the appearance of clinical end-stage motor signs in Prnp-h[A53T]αS (red curve, median 447 days, n = 15), Thy1-h[A53T]αS (black curve, median 221 days, n = 15), Thy1-h[A30P]αS (blue curve, median 580 days, n = 15), and Thy1-mαS (orange curve, median 242 days, n = 15). When survival times of TG lines were compared to each other pair-wise, statistically significant differences were found (Log-rank test, p < 0.0001) except for Thy1-h[A53T]αS vs. Thy1-mαS. (b) Disease duration starting from onset of motor signs until end-stage phenotype in Prnp-h[A53T]αS (red, median 7 days), Thy1-h[A53T]αS (black, median 18 days), Thy1-h[A30P]αS (blue, median 33 days), and Thy1-mαS (orange, median 21 days). When disease durations of TG lines were compared to each other pair-wise, only Prnp-h[A53T]αS and Thy1-h[30P]αS lines had a statistical difference in their disease duration (One-way ANOVA, Bonferroni’s multiple comparison test, p < 0.0001). (c) Immunostaining of inclusions labeled with the p-αS antibody, which recognizes phosphorylated αS at serine 129, in Prnp-h[A53T]αS, Thy1-h[A53T]αS, Thy1-h[A30P]αS, and Thy1-mαS mice. Nuclear fast red was used as counterstain. Representative sagittal sections of the midbrain from 12-, 7.3-, 20.8-, and 8.3-month-old mice, respectively, are shown. Scale bars, 50 μm and 20 μm (insert). (d) Representative images of pFTAA-positive inclusions in the brainstem of terminally ill Prnp-h[A53T]αS, Thy1-h[A53T]αS, Thy1-h[A30P]αS, and Thy1-mαS mice. Scale bars, 50 μm and 20 μm (insert). (e) Fluorescence double-staining for p-αS (red) and ThioS (green) of brainstem pathology in Thy1-h[A30P]αS. Examples of p-αS-positive inclusion (arrowhead outlines) and ThioS-positive aggregate (white arrowheads) are shown in high magnification (inserts). (f) Fluorescence double-staining for p-αS (red) and pFTAA (green) of brainstem pathology in Thy1-h[A30P]αS. Note that many of the pFTAA-positive inclusions are not co-labeled with the p-αS antibody. Examples of a p-αS/pFTAA-double-positive inclusion (arrowhead outline) and a pFTAA-positive deposit in absence of p-αS signal (white arrowhead) are in high magnification (inserts). (g) Percentage of pFTAA-positive inclusions that are lacking p-αS signal. A similar proportion of non-overlapping pFTAA signal among the lines was found (n = 3 mice per mouse line). Results are expressed as mean ± SEM