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. 2017 Sep 27;37(39):9361–9379. doi: 10.1523/JNEUROSCI.0084-17.2017

Figure 5.

Figure 5.

Low-dose AAV-mediated overexpression of RGMa in the mouse SN results in a mild but progressive induction of motor behavioral deficits. A, A significant increase in front paw placement errors was observed in the grid test in the RGMa group (red) compared with the three control groups (AAV-Empty, blue; AAV-GFP, green; and saline, black) (p < 0.0001, F(3,400) = 61.31). Post hoc testing showed an increase in error rates in RGMa-overexpressing mice from 3.5 weeks after surgery compared with all three control groups (black asterisks) with some variation at different testing time points (red asterisks). B, Hindlimb placement was measured by the narrow beam test. Mice treated with AAV-RGMa showed small but significant increased error rate in this test compared with the controls (p = 0.0002, F(3,416) = 6.586). C, Preference of bilateral or unilateral front paw use was measured in a cylinder test. The ratio of right paw use over total rearing events was determined. RGMa-overexpressing mice progressively increased their preference for only right paw use compared with control groups (p < 0.0001, F(3,375) = 12.37). Post hoc testing indicated more right paw use in RGMa animals compared with either one or two control treatment groups (red asterisks) or to all control groups (black asterisk) starting from 8 weeks after surgery. D, The swing test revealed no significant differences in the rotation preference of the mice between any of the treatment groups. E, Tremor was observed in RGMa-overexpressing mice (p < 0.0001, F(3,416) = 20.71) starting at 3.5 weeks after surgery. F, None of the treatment groups showed any significant differences in weight gain. For all tests, week 0 is the baseline measurement performed 2 d before the AAV injection. Each treatment group includes 7–8 animals per quantification, with the saline group containing 6 animals. Statistical analysis was performed with a two-way ANOVA with Tukey's post hoc multiple testing correction: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. All data are expressed as mean with bars representing SEM.