Figure 6. Scn8a Heterozygosity Enhances a More Severe Axonal Neuropathy Model, Gars^P278KY/+.

(A) There was no additional reduction in axon diameter in the motor branch of the femoral nerve over Gars^P278KY/+ in mice also heterozygous for Scn8a.

(B) The Gars^P278KY/+ mice have fewer myelinated axons, but this reduction was not exacerbated by Scn8a heterozygosity.

(C) NCV was further reduced in double heterozygotes, beyond the effects of Gars^P278KY/+ alone.

(D) Additional muscle atrophy was present in double-heterozygous mice.

(E) Additional defects were present at NMJs, with increased denervation and partial innervation, and virtually no fully innervated junctions.

Analyses were performed on eight mice of each genotype between 2.5 and 3.5 months of age, except (C), in which eight control and nine Scn8a^+/− mice were used, and results from one Gars^P278KY/+ and two double-heterozygous mice were not included because a reliable EMG signal and conduction velocity could not be ascertained. Values in (B)–(E) are mean ± SD. An approximately equal mix of male and female mice were used. *p < 0.05, **p < 0.01 ***p < 0.001, ****p < 0.0001.