Figure 1. Plp-CreERT; Mek1DD/+ mice demonstrate increased myelin thickness as a result of the addition of new myelin wraps to existing myelin sheaths. A, Matched corpus callosum (CC) sections from adult WT;Mek1DD/+ (WT) and Plp-CreERT;Mek1DD/+ (MUT) mice at 2 mpi stained with CC1 (green) and pERK (red). Scale bar, 25 μm. B, Quantification confirms a significant increase in the percentage of CC1+ cells that colabeled with pERK in MUT mice in both spinal cord (SC) and CC. C, Quantification of the total number of CC1+ mature OLs in the dorsal column of the SC and the CC at 2 mpi demonstrates no significant difference between WT and MUT mice. D, Matched SC and CC sections immunolabeled with anti-PLP reveal enlargement of white matter structures in MUT mice. Arrows point to expanded areas of the CC. Scale bars, 500 μm. E, Electron micrographs of SC and CC show increased myelin thickness in MUT mice compared with control littermates at 21 dpi and at 2 mpi. Arrows indicate example axons of similar diameter. Scale bar for SC, 2 μm; CC, 1 μm. F, High-magnification electron micrographs reveal that the additional myelin wraps seen in MUT mice appear ultrastructurally normal. Scale bar, 100 nm. G, H, Analysis of SC electron micrographs by g-ratio calculation shows significantly decreased g-ratios (thicker myelin) in both 21 dpi MUT (pink) and 2 mpi MUT (red) mice compared with WT (blue) controls, with a significant decrease from 21 dpi to 2 mpi. I, J, g-ratio calculation from CC electron micrographs indicates significantly decreased g-ratios in both 21 dpi MUT (pink) and 2 mpi MUT (red) mice compared with WT (blue) controls. K, Analysis of optic nerve (ON) EM shows significantly decreased g-ratios in 2 mpi MUT (red) mice compared with WT (blue) controls. L, Average ON g-ratios show overall significantly decreased g-ratios observed in MUT (red) mice versus WT (blue) controls. M, Examining the number of unmyelinated axons in SC and CC electron micrographs shows no difference between WT (blue) and 2 mpi MUT (red) mice. ****p < 0.0001, ***p < 0.001, *p < 0.05. Data are shown as mean ± SEM. At least three mice per genotype were used for all analyses; at least 100 axons per mouse were analyzed for g-ratio calculations.