Gpr56 mutant mice show progressive accumulation of myelin abnormalities. (A–C) TEM images of SNs from (A) WT (n = 3), (B) Gpr56^+/− (n = 3), and (C) Gpr56^−/− (n = 4) mice on P90. (D–F) TEM images of SNs from (D) WT, (E) Gpr56^+/−, and (F) Gpr56^−/− mice on P180 (n = 3 animals per genotype). (G–I) TEM images of SNs from (G) WT, (H) Gpr56^+/−, and (I) Gpr56^−/− mice on P300 (n = 3 animals per genotype). Red arrowheads denote abnormal myelin profiles. Black arrows mark Schmidt-Lanterman incisures. Black box highlights myelin debris observed by P300. (A–I) Bar, 2 µm. (J–O) SC defects and pathologies observed in Gpr56 heterozygous and mutant peripheral nerves included bands of Büngner (J; bar, 500 nm), aberrant myelination of other SCs (K; bar, 2 µm), abnormal cytoplasmic protrusions (L; bar, 500 nm), myelinated Remak bundles (M; bar, 4 µm), minifascicles (N; bar, 2 µm), and myelin debris accumulation (O; bar, 2 µm). (P) Two-way ANOVA analysis revealed a significant interaction between age and genotype (****, P < 0.0001). Dunnett's multiple comparisons test also showed significant increases in the percent of axons with abnormal myelin profiles in Gpr56^+/− and Gpr56^−/− animals compared with WT at each time point (****, P < 0.0001). (Q–S) No significant differences between total myelinated axon number in WT and Gpr56^−/− (P90: P < 0.15; P180: P < 0.44; P300: P < 0.89), nor between Gpr56^+/− and Gpr56^−/− (P90: P < 0.14; P180: P < 0.13; P300: P < 0.52) at any stage. Unpaired Student’s t test. (P–S) Error bars represent SEM.