Figure 5. Axonal Neuropathy Is Exacerbated by Partial Impairment of NaV1.6/Scn8a^+/−.

(A–D) Cross-sections from the motor branch of the femoral nerve for control (A), Scn8a^+/− (B), Gars^C201R/+ (C), and double-heterozygous mice (D); note (A) and (B) are montages to capture the entire nerve.

(E) Axon diameters were not changed in Scn8a^+/−, and double-heterozygous mice did not show a greater reduction in axon diameters than Gars^C201R/+ alone.

(F) Axon number in the motor branch of the femoral nerve was unchanged in any genotype.

(G) NCV was mildly reduced in Scn8a^+/− mice, and double heterozygotes had conduction velocities reduced below either single mutant.

(H) No muscle atrophy was observed in Scn8a^+/− mice, and no additional muscle atrophy beyond the effects of Gars^C201R/+ was observed in double heterozygotes.

(I) Scn8a^+/− mice did not show changes in innervation at the NMJ, but double-heterozygous mice had more partial innervation and denervation at NMJs than Gars^C201R/+ mice.

Values in (F)–(I) are mean ± SD. Analyses were performed on eight mice per genotype at 3 months of age with an approximately equal mix of males and females.

*p < 0.05, **p < 0.01. Scale bar in (D), 50 μm for (A)–(D).