Fig. 1: Med23Q649R mutation disrupts OL maturation.
a Strategy for the generation of OL lineage-specific Med23Q649R mutant mice. b Sanger sequencing of the Q649R mutation on the Med23 mutant allele. c Photographs showing optic nerves of control and Med23Q649R mice at P14. Scale bar: 1 mm. d–f Representative electron micrographs of optic nerves in control and Med23cKO mutants at P14. Scale bars: 2 μm. The percentage of myelinated axons is shown in e, and the myelin g-ratio scatterplot vs axon diameters is quantified in f (n = 3). g, h In situ hybridization for Mbp and Plp1 in the spinal cord (SC), forebrain (FB), and cerebellum (CB) from control and Med23Q649R mice at P7. Scale bars: 100 μm. i Cartoon depicting stereotype stages of OL morphology changes during differentiation in culture. j Representative micrographs showing control and Med23Q649R OLs that were in differentiation medium for 0 day and 3 days in culture. Scale bars: 50 μm. k OPCs isolated from control and Med23Q649R mice were cultured in differentiation medium for 3 days. The cells were stained for Olig2 (red) and NG2 (green) at day 0, CNP (red) and NG2 (green) at day 1, and MBP (red) and Olig2 (green) at day 3. Scale bars: 50 μm. l Quantification of the percentage of CNP+ cells among total DAPI+ cells in control and Med23Q649R OLs after 1 day of differentiation (n = 3). m Quantification of the percentage of MBP+ cells among total DAPI+ cells in control and Med23Q649R OLs after 3 days of differentiation (n = 3). n Comparison of spontaneous alternation percentage (left) and total entry (right) in the Y-maze test between the control and Med23Q649R adult mice (n = 9). o Comparison of the preference index for a novel object in the 2-object novel object recognition test between the control and Med23Q649R adult mice (n = 9). The data are presented as the mean ± SEM; two-tailed unpaired Student’s t-test; ns > 0.05; *P < 0.05, **P < 0.01, and ***P < 0.001.
