SARM1-CDN protects from AxD in vivo with efficacy similar to SARM1-KO. (A and B) Representative photomicrographs of toluidine blue–stained semithin cross sections of the right sural nerve 5 d after transection of the sciatic nerve in mice injected with vector (A; n = 4) or SARM1-CDN (B; n = 5). A′ and B′ show enlargements of areas indicated by rectangles in A and B. The arrow and arrowhead indicate lipid-laden histiocytes and myelin debris, respectively. (C and D) Representative electron micrographs of the right sural nerve of a mouse injected with EGFP vector showing complete loss of internal nerve architecture (C) whereas unmyelinated (asterisks) and myelinated axons are preserved after SARM1-CDN injection (D). C′ and D′ show enlargements of areas indicated by rectangles in C and D. (E and F) All axons in cross sections of the entire sural nerve were counted in wild-type mice injected with vector (n = 4 in E; n = 3 in F) or SARM1-CDN (n = 5 in E, n = 3 in F) or in SARM1-KO mice (n = 5 in E and F) and expressed as percentage of axon numbers of the respective intact contralateral sides at 5 (E) and 10 (F) d after transection. Data are presented as mean ± SE (SEM), tested with a one-way ANOVA, which shows significant main effects in E (F(2,11) = 97.13, P < 0.0001; post hoc Tukey’s multiple comparison test shows vector versus SARM1-SARM1-CDN, ****, P < 0.0001; vector versus SARM1-KO, ****, P < 0.0001; SARM1-CDN versus SARM1-KO, P = 0.5953) and F (F(2,8) = 20.73; P = 0.0007; Tukey’s multiple comparison test shows vector versus SARM1-CDN, **, P = 0.0077; vector versus SARM1-KO, ***, P = 0.0005; SARM1-CDN versus SARM1-KO, P = 0.2543). n.s., not significant. (G) Representative micrographs of toluidine blue–stained sections of the sural nerve 10 d after cut. Bottom row displays enlargements of indicated areas in the images above. Bars, 50 µm (A and B), 10 µm (A′ and B′), 5 µm (C and D), 1 µm (C′ and D′), 50 µm (G, top), and 10 µm (G, bottom).