Figure 2.

Motor nerve electrophysiology and representative waveforms in SAPP. The mean dorsal caudal tail (A–C) and sciatic (D–F) motor nerve electrophysiological studies of a cohort of B7-2 WT and B7-2 KO mice, grouped by age is shown. A reduction in mean dorsal caudal tail motor conduction velocity starts at 20–23 weeks of age in B7-2 KO mice compared to B7-2 WT controls (B), implying that demyelination of large myelinated axons is the earliest feature of SAPP. Reduction in mean CMAP amplitude and increase in total CMAP duration become apparent by 24–27 weeks of age (A, C), implying associated axonal injury and further demyelination of small- and medium-sized axons, respectively. Significant changes in these parameters in the sciatic nerves occur between 24 and 27 weeks (D–F), implying diffuse demyelination with axonal injury/loss. There are no statistically significant changes in these electrophysiological parameters in B7-2 WT mice. The progressive reductions in mean CMAP amplitude and conduction velocity reach a nadir, and the increase in total CMAP duration reaches a peak between 32 and 35 weeks age. There are small but significant increases in conduction velocity and reduction in total CMAP duration between 36 and 39 weeks of age, suggesting axonal remyelination in both nerves. There is no significant change in mean dorsal caudal tail nerve CMAP amplitudes between 36 and 39 weeks of age; however, a statistically significant increase in sciatic nerve CMAP amplitudes is observed, suggesting some degree of axonal regeneration or resolution in distal conduction block. * indicates p < 0.05 relative to age-matched B7-2 WT and <20-week-old B7-2 KO mice, ^† indicates p > 0.05 between 32–35 week and 36–39 week data, and ^ indicates p < 0.05 between 32–35 week and 36–39 week data. Representative distal (upper) and proximal (lower) CMAP waveforms from the dorsal caudal tail nerve (DCTN) and sciatic nerve of a female B7-2 KO mouse with SAPP at peak severity (G and I, respectively) are compared with an age-matched unaffected B7-2 WT mouse (H and J). There are reductions in CMAP amplitudes and increases in total waveform durations in SAPP compared to controls. The reduction in CMAP amplitudes is generally uniformly diffuse in the sciatic nerves (I), while approximately 25%–50% reduction in proximal amplitudes compared to distal responses is commonly observed in the DCTN (G), suggesting a component of conduction block between distal and proximal stimulation sites. Numbers to the upper left depict sensitivity in mV per division (mV/D), numbers to the upper right depict sweep speed in ms per division (ms/D) while numbers above each waveform to the right represent supramaximal stimulus current (in mA).