Fig. 4: (GR)400 and (PR)400 knock-in mice develop age-dependent lower motor neuron loss and progressive rotarod impairment.
a, Body weights of WT, (GR)400 and (PR)400 male mice up to 12 months of age. Graph, mean ± s.e.m., n = 14 mice per genotype, two-way ANOVA, Bonferroni’s multiple comparison. NS denotes P > 0.05. b, Accelerated rotarod analysis of motor coordination in WT, (GR)400 and (PR)400 male mice up to 12 months of age. Graph, mean ± s.e.m., n = 14 mice per genotype, two-way ANOVA, Bonferroni’s multiple comparison. NS denotes P > 0.05. c, Panel shows representative image of Nissl staining of lumbar spinal cord in WT mice; the dashed red line delineates the sciatic motor pool in which motor neurons were counted. n = 5 mice per genotype. d, Quantification of Nissl-stained motor neurons in lumbar spinal cord region L3–L5 in WT, (GR)400 and (PR)400 mice at 6 months of age. Graph, mean ± s.e.m., n = 5 mice per genotype, one-way ANOVA, Bonferroni’s multiple comparison. NS denotes P > 0.05. e, Quantification of Nissl-stained motor neurons in lumbar spinal cord region L3–L5 in WT, (GR)400 and (PR)400 mice at 12 months of age. Graph, mean ± s.e.m., n = 5 mice per genotype, one-way ANOVA, Bonferroni’s multiple comparison. f, Representative EDL MUNE traces from 12-month-old WT (left panel), (GR)400 (center panel) and (PR)400 (right panel) mice. Peaks correspond to physiological recruitment of motor units following electrical stimulation; n mice = 5 WT, 6 (GR)400 and 6 (PR)400; n muscles = 8 WT, 12 (GR)400 and 9 (PR)400. g, Quantification of MUNE determined in EDL muscle in WT, (GR)400 and (PR)400 mice at 12 months of age. Graph, mean ± s.e.m.; n mice = 5 WT, 6 (GR)400 and 6 (PR)400; n muscles = 8 WT, 12 (GR)400 and 9 (PR)400; one-way ANOVA, Bonferroni’s multiple comparison. MN, motor neuron.
