Figure 5.

Rapid Wallerian degeneration in W258AWld^S Tg mice. (A) Brain Western blots from W258AWld^S Tg, Wld^S, and wild-type mice probed with Wld18. W258AWld^S lines 2 and 4 express a 43-kD band, which is absent in wild type. (B) Wld18 immunofluorescence (red) of lumbar spinal cord. Motor neuron nuclear signal strength and distribution in W258AWld^S lines match Wld^S heterozygotes. Identical laser intensities and camera settings were used for each image. (C) Nmnat1 activity is unaltered in the W258AWld^S brain. (D, i and ii) Semithin sections of W258AWld^S distal sciatic nerve 72 h after lesion. Axons are degenerated, similar to wild-type or ΔN16Wld^S axons (Fig 2). (iii–vi) In mice crossed to YFP-H, tibial nerve axons lose continuity within 72 h of sciatic lesion, except in Wld^S (iii). (E) SCG explants untreated (i–iv) or treated (v–viii) with 100 nM FK866 for 72 h and then cut. Unlike wild-type axons (i, ii, v, and vi), untreated Wld^S axons are intact 72 h after being cut (iv) but when treated with FK866 are more degenerated (viii). (F) Quantification of continuous neurites (or neurite bundles). ***, P < 0.0001 (one-way analysis of variance followed by Bonferroni post-hoc test); n = 8 (wild type [WT]) and 9 (Wld^S). (G) NAD⁺ or NADP⁺ levels in wild-type and Wld^S explants ± FK866 at 1–100 nM. Mean of three different experiments. (C, F, and G) Mean ± SD. Bars: (B, D, i and ii, and E) 10 µm; (D, iii–vi) 100 µm.