Figure 1.

Progressive Locomotor Dysfunction and Hindlimb Muscle Atrophy in Nmnat2^gtE/gtE;Wld^S/S Mice, but Not Nmnat2^gtE/gtE;Sarm1^−/− Mice

(A and B) Latency to fall in an accelerating Rotarod task for mice of the indicated genotypes and ages. Means ± SEM are plotted (maximum test duration, 300 s) for n = 7/8 male mice of each genotype (A) (^∗∗∗p < 0.001 in two-way ANOVA with Dunnett’s multiple comparisons) and n = 7 female mice of each genotype (B) (NS, not significant [p = 0.29] in t test).

(C) Representative transverse sections of gastrocnemius muscle for mice of the selected genotypes and ages (as indicated) stained with H&E. Modest fiber atrophy is seen in Nmnat2^gtE/gtE;Wld^S/S gastrocnemius at 10 weeks, and more severe atrophy, with centrally located nuclei, hypertrophic fibers (^∗), and pyknotic nuclear clumps (arrow), is evident at 10 months. Images are representative of male and female mice at 10 weeks and 8–12 months but just female mice at 24 months.

(D and E) Gastrocnemius muscle weights for mice of the indicated genotypes and ages. Individual animal values with means ± SEM are plotted for n = 3–5 male mice per group (D) (^∗p < 0.05 and ^∗∗∗p < 0.001 in one-way ANOVA with Tukey’s multiple comparisons; NS, not significant) and n = 4–5 female mice per group (E) (^∗p < 0.05 in t test).

See also Movies S1, S2, S3, S4, S5, and S6, Table S1, and Figure S1.