Figure 4. Qk deletion in oligodendrocyte precursor cells leads to defective myelinogenesis without impairing differentiation of Aspa⁺ myelinating oligodendrocytes.

(A) Schema of the generation of Qk-Plp-iCKO mice. (B) Representative images of severe hind limb paresis in Qk-Plp-iCKO mice 2 weeks after tamoxifen injection. (C) Latency of mice falling off the rotarod at a constant speed (5 rpm). n = 3 mice in the Qk-Plp-iCKO group; n = 7 mice in the control group. (D) Body weights of Qk-Plp-iCKO mice (n = 12) and control mice (n = 18) 2 weeks after tamoxifen injection. (E) Kaplan–Meier curves of and log-rank test results for overall survival in Qk-Plp-iCKO mice (n = 32) and control mice (n = 59). (F) Representative images of and quantification of immunofluorescent staining of MBP, GFP, and Iba1 in the corpus callosum tissues in Qk-Plp-iCKO mice (n = 6) and control mice (n = 3) 2 weeks after tamoxifen injection. Scale bars, 50 μm. (G) Representative images of and quantification of staining of FluoroMyelin in the corpus callosum tissues in Qk-Plp-iCKO mice (n = 3) and control mice (n = 4) 2 weeks after tamoxifen injection. Scale bars, 50 μm. (H) Representative electron micrographs of and quantification of the percentage of myelinated axons in the optic nerves in Qk-Plp-iCKO mice (n = 3) and control mice (n = 5) 2 weeks after tamoxifen injection. Scale bars, 500 nm. (I) Representative images of and quantification of immunofluorescent staining of Aspa and Qki in the corpus callosum tissues in Qk-Plp-iCKO mice (n = 3) and control mice (n = 4) 2 weeks after tamoxifen injection. Scale bars, 50 μm. Data are shown as mean ± s.d. and were analyzed using Student's t test (C,D, F–H) or one-way ANOVA with Tukey’s multiple comparisons test (I). **p<0.01; ****p<0.0001; ns: not significant.

Figure 4—figure supplement 1. Deletion of Qk in mouse oligodendrocyte precursor cells results in hypomyelination in the central nervous system.

(A) Kaplan–Meier curves of and log-rank test results for quaking phenotype-free survival of Qk^L/L mice (n = 8), Plp-CreER^T2;WT mice (n = 8), Plp-CreER^T2;Qk^L/+ mice (n = 43), and Plp-CreER^T2;Qk^L/L mice (n = 32). (B) Representative electron micrographs of and quantification of the g-ratio in the optic nerves in Qk-Plp-iCKO mice (n = 3) and control mice (n = 5) 2 weeks after tamoxifen injection. Scale bars, 2 μm. (C–E) Quantification of the g-ratio (C) axonal diameter (D) and density of axon (E) in the mice in (B). Data are shown as mean ± s.d. and were analyzed using Student's t test. *p<0.05; ns: not significant. (F) Representative images of and quantification of immunofluorescent staining of GFP and Pdgfrα in the cortex tissues in Qk-Plp-iCKO;mTmG mice (n = 6) and control Plp-CreER^T2;mTmG mice (n = 3) 2 weeks after tamoxifen injection. Scale bar, 50 μm. Data are shown as mean ± s.d. and were analyzed using Student's t test. ns: not significant.

Figure 4—figure supplement 2. Deletion of Qk does not alter proliferation of oligodendrocyte precursor cells and oligodendroglial lineage cells.

(A, B) Representative images of and quantification of immunofluorescent staining of Pdgfrα and Ki67 (A) and Olig2 and Ki67 (B) in the brain region within the red dotted box in Qk-Plp-iCKO;mTmG mice (n = 6 in A and n = 4 in B) and control Plp-CreER^T2;mTmG mice (n = 6 in A and n = 4 in B) 2 weeks after tamoxifen injection. Scale bar, 50 μm. Data are shown as mean ± s.d. and were analyzed using Student's t test. ns: not significant. Arrow indicates Pdgfrα⁺Ki67⁺ cells (A) and Olig2⁺Ki67⁺ cells (B).