Figure 2

Canonical Wnt signaling changes in wild type, LRRK2 KO and LRRK2 G2019S KI mice in vivo over time. Mice were injected intracranially at P0 with a lentiviral biosensor for TCF/LEF to detect Wnt signaling activities. Repeated measures of the resulting bioluminescence signal were detected over a period of 28 weeks in wild type (WT), LRRK2 knockout (KO) and LRRK2 G2019S knock-in (KI) mice. Data is shown as mean relative luciferase activity ± SEM, normalized to WT set to one (A, B, and C). Sex separation reveals differences between LRRK2 genotypes for only male (B) and only female mice (C). The effect of time is shown as mean relative luciferase activity ± SEM, normalized to week one set to one for each individual LRRK2 genotype (D, E, and F). Sex related differences are represented as mean raw luciferase signal ± SEM in photons per seconds (G). Wnt signaling changes in WT, KO and KI half brain protein samples are shown as relative protein level for active β-catenin (ABC) in relation to total β-catenin (H–M). Data is shown as fold-change to WT and β-actin served as loading control. Statistical significance, indicated as ****P < 0.0001 and *P < 0.05 was tested for genotype differences and effect of time by mixed-effects analysis, and the impact of sex on basal in vivo Wnt signaling was analyzed by unpaired t-test with Welch’s correction. Immunoblot experiments were tested via unpaired t-test with Welch’s correction with n = 16, 8 males and 8 females. The original Western Blot images corresponding to Fig. 2 H-M are shown in the Supplementary Material 1 page 5.