Fig. 2

Glial Neuregulin-1 (NRG1) ablation improves neuropathic symptoms in adult CMT1A mice. a Rotarod analysis of 3-month-old mice on 4 consecutive days (wild type n = 7, NRG1cKO n = 8, CMT1A n = 7, CMT1A-NRG1cKO n = 8, two-way analysis of variance (ANOVA) with Tukey’s multiple comparison tests). b The foot print length in 4-month-old CMT1A (n = 7), wild type (n = 6), NRG1cKO (n = 6), and CMT1A-NRG1cKO (n = 7) mice. c Representative electrophysiological traces of sciatic nerve recordings of 4-month-old wild-type, NRG1cKO, CMT1A and CMT1A-NRG1cKO mice after distal (d) and proximal (p) stimulation (up arrow: stimulus artefact, down arrow: distal motor latencies). d Quantification of nerve conduction velocity (NCV) in 4-month-old wild type (n = 7), NRG1cKO (n = 12), CMT1A (n = 16), and CMT1A-NRG1cKO (n = 9) mice. e Quantification of compound muscle action potential (CMAP) from mice analyzed in d. f Quantification of temporal dispersion as measured by CMAP duration in 4-month-old wild type (n = 12), NRG1cKO (n = 16), CMT1A (n = 12), and CMT1A-NRG1cKO (n = 11) mice. The average values from four stimulations (distal and proximal from both sides) were calculated per mouse. g Representative light microscopic images of sciatic nerve cross-sections from 4-month-old wild-type, CMT1A, and CMT1A-NRG1cKO adult mice (left panels, scale bar 5 µm). Quantification of the number of myelinated axons per sciatic nerve cross-section (right panel) in wild type (n = 7), CMT1A (n = 6), and CMT1A-NRG1cKO (n = 7) mice. h Representative electron micrographs of sciatic nerve cross-sections from 4-month-old mice (left panels), demonstrating hypermyelination (arrows) of small caliber axons in CMT1A compared to wild-type and CMT1A-NRG1cKO mutants (scale bar 2.5 µm). Quantification of the mean myelin sheath thickness (g-ratio) (right panel, wild type n = 5, NRG1cKO n = 5, CMT1A n = 5, CMT1A-NRG1cKO n = 5, 221–375 fibers were measured per animal). i Myelin sheath thickness (g-ratio, data of f) plotted against the axon diameter shows hypermyelination of small to mid-caliber and hypomyelination of large caliber fibers in CMT1A mice compared to controls (NRG1cKO, left panel). Ameliorated hypermyelination of small to mid-caliber axons is visible in CMT1A-NRG1cKO mice when compared to CMT1A mice (right panel). j Electron micrograph of an onion bulb structure in sciatic nerves of a 4-month-old CMT1A mouse (scale bar 1 µm). k Quantification (right panel) of onion bulb structures per area (15,740 µm²) in cross-sections of sciatic nerve of 4-month-old mice (wild type n = 4, NRG1cKO n = 6, CMT1A n = 6, CMT1A-NRG1cKO n = 6). Source data are provided as a source data file. All respective p-values are depicted as a range of significance with *p < 0.05 and ***p < 0.001; b, d, e–h, k: one-way ANOVA, Tukey’s post test