Fig. 6

Mef2c-KD shows motor neuron disease-like behaviors in mice. (A) A scheme illustrating delivery of AAV-shRNA-Control-GFP (shControl) or AAV-shRNA-Mef2c-GFP (shMef2c) viruses into the cortical layer V of WT mice and performing longitudinal behavioral study 3, 6 and 9 weeks after injection. (B) Representative still images of the tail suspension test for shControl and shMef2c-transduced mice. (C) The number of forelimbs clasping in tail suspension test in 3-, 6- and 9-weeks post-injection. Statistics were calculated using repeated measures ANOVA (N = 5 mice/group for shControl and shMef2c) (3weeks, P = 0.51; 6 and 9weeks, ***, P < 0.001). (D) Aggregated coordinate plots in the first 10 s of tail suspension test for shControl and shMef2c-transduced mice. (E) A representative still image of the inverted grid test. Right: the minimal holding impulse. Statistics were calculated using repeated measures ANOVA (N = 5 mice/group for shControl and shMef2c) (3weeks, P = 0.387; 6weeks, P = 0.37; 9weeks, P = 0.848). (F)  A representative still image of the accelerated wheel test. Bottom: the computer-assisted footprint in wheel running test for a representative mouse in each group. (G) Gait analysis showed shorter stride length and wider stride width in shMef2c mice. Statistics were calculated using repeated measures ANOVA (N = 5 mice/group for shControl and shMef2c, n = 10 steps/mouse). Significantly different at *, P < 0.05; **, P <0.01. Error bars represent means ± SEM. (H) A scheme proposing how MEF2C enhancer SNP impairs MEF2C transcription, resulting in mitochondrial dysfunction and inducing oxidative stress which makes motor neuronal damage and motor deficit. Scheme created with BioRender.com