Fig. 8: Functional improvement of the R6/2 mice following in vivo cell conversion. | Nature Communications

Fig. 8: Functional improvement of the R6/2 mice following in vivo cell conversion.

From: Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington’s disease

Fig. 8

a Representative footprint tracks among wild-type littermates, R6/2 mice, R6/2 mice treated with control viruses or NeuroD1 + Dlx2 viruses. Dashed lines indicate stride length (L) and width (W). b, c Quantified data of stride length (b) and width (c) among different groups. The stride length decreased in R6/2 mice, but partially rescued by NeuroD1 plus Dlx2 treatment (one-way ANOVA with Bonferroni’s post hoc test). d Representative tracks showing locomotor activity in the open field test (20 min) among different groups. e Quantified data showing the total travel distance reduced in R6/2 mice but partially improved by NeuroD1 plus Dlx2 treatment (one-way ANOVA with Bonferroni’s post hoc test). **p < 0.01, ***p < 0.001. f Average body weight of R6/2 mice at 7 days before surgery and 30 days after surgery (viral injection). NeuroD1 plus Dlx2-treated R6/2 mice showed less body weight loss than the control virus-treated mice at 30 dpi (*p < 0.05, unpaired Student’s t-test). Mouse number in each group is labeled in each bar. g Typical clasping (top) and non-clasping (bottom) phenotype in the R6/2 mice. h The percentage of mice showing clasping phenotype was decreased in NeuroD1 plus Dlx2-treated R6/2 mice (*p < 0.05, 2-sided Pearson Chi-square test). i The average clasping score was also significantly reduced by NeuroD1 plus Dlx2 treatment (*p < 0.05, unpaired Student’s t-test). Mouse number in each group is labeled in the bar. j The grip strength of R6/2 mice did not change following NeuroD1 plus Dlx2 treatment. k Experimental diagram showing survival rate calculation from 7 days post-surgery to 38 days post surgery (endpoint mouse age: P98). Mice that died between 7 and 38 dpi were recorded. Behavioral tests were conducted between 30–37 dpi. l Kaplan–Meier survival graph showing that 13 out of 29 R6/2 mice died in the control virus group, whereas only 2 out of 33 R6/2 mice died in the NeuroD1 plus Dlx2 treatment group (p < 0.001, 2-sided Pearson Chi-square test). Data are shown as mean ± SEM in panel b, e and i. Data in panel ec, f and j are shown as box plot (boxes, 25-75%; whiskers, 10-90%; lines, median).

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