Fig. 5
From: Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients
Persistent neuroinflammation and axon loss in mice injected intrathecally with a SARM1V184G AAV construct. This figure demonstrates anatomical findings from the larger subset of mice with slower onset pathology. (A) The normalized average number of cells stained by the macrophage marker anti-CD68 in nerve, and the average percent area of total anti-CD68 staining in nerve and in spinal cord sections, from C57BL/6 mice injected with a SARM1V184G (n = 7) AAV construct relative to those injected with a human SARM1 reference allele construct (n = 8) 12 weeks post-injection; *p < 10− 4 difference from reference allele. (B) Representative images of sural nerve stained with DAPI and anti-CD68 from mice 12 weeks after injection with a SARM1V184G or reference allele construct. White arrows indicate CD68-positive activated macrophages. (C) Representative images of toluidine blue stained sural nerve sections. (D) Average fibers per cross-sectional μm2 in sural, sciatic and tibial nerves from mice 12 weeks after injection with a SARM1V184G (n = 7 mice) or reference allele construct (n = 8); *p < 0.05, **p < 0.001. (E) Average g-ratio (ratio between the inner and outer myelin sheath) for axons in the sural, sciatic and tibial nerves from mice 12 weeks after injection with a SARM1V184G or reference allele construct. These analyses demonstrate that mice injected with SARM1V184G exhibit axon loss and persistent neuroinflammation in their nerves 12 weeks after infection, compared to mice injected with a control SARM1 construct