Myrf haploinsufficiency suppresses myelin phenotypes in Fbxw7 mutant models. a Representative images of optic nerves from Fbxw7fl/fl, Plp1-CreERT-Fbxw7fl/fl, and Plp1-CreERT-Fbxw7fl/fl; Myrf fl/wt mice at 3-months post-TAM stained for MYRF. b Representative images of cerebellums from Fbxw7fl/fl, Plp1-CreERT-Fbxw7fl/fl, and Plp1-CreERT-Fbxw7fl/fl; Myrf fl/wt mice at 6-months post-TAM stained for MYRF, MBP, and NeuN. c Representative images of myelin internodes in layer I of the pSS in Fbxw7fl/fl, Plp1-CreERT-Fbxw7fl/fl, and Plp1-CreERT-Fbxw7fl/fl; Myrf fl/wt mice at 6-months post-TAM stained with MBP (magenta), CNP1 (green), and CASPR (cyan). d Representative images of the spinal cords of fbxw7vo86/vo86 and fbxw7vo86/vo86; myrfue70/WT zebrafish on Tg(mbp:eGFP-caax) and Tg(mbp:nls-eGFP) transgenic backgrounds at 3 dpf. e Quantification of nuclear MYRF intensity in Fbxw7fl/fl (N = 4), Plp1-CreERT-Fbxw7fl/fl (N = 3), and Plp1-CreERT-Fbxw7fl/fl; Myrf fl/wt (N = 3), normalized to controls at 3-months post-TAM in the optic nerve. Data shown as mean ± SEM. Statistical significance determined by two-way ANOVA with Tukey’s multiple comparisons test. f Quantification of nuclear MYRF intensity in Fbxw7fl/fl (N = 4), Plp1-CreERT-Fbxw7fl/fl (N = 3), and Plp1-CreERT-Fbxw7fl/fl; Myrf fl/wt (N = 4), normalized to controls at 6- months post-TAM in the cerebellum. For both e and f, small dots represent individual cell intensities, larger dots represent animal means ± SEM with Tukey’s multiple comparisons test. Statistical significance determined by one-way ANOVA on animal means. g Quantification of myelin outfolds in layer I of the pSS in Fbxw7fl/fl (N = 6), Plp1-CreERT-Fbxw7fl/fl (N = 6), and Plp1-CreERT-Fbxw7fl/fl; Myrffl/wt (N = 4) mice at 6-months post-TAM. Data shown as mean ± SEM, each datapoint represents mean from an individual animal. Statistical significance determined by two-way ANOVA, with Tukey’s multiple comparisons test. h Quantification of NeuN+ cells wrapped in MBP+ membrane in the granule layer of the cerebellum of Fbxw7fl/fl and Plp1-CreERT-Fbxw7fl/fl mice at 3- and 6- months post-TAM. Fbxw7fl/fl (3 m: N = 7, 6 m: N = 5), Plp1-CreERT-Fbxw7fl/fl (3 m: N = 6, 6 m: N = 6), and Plp1-CreERT-Fbxw7fl/fl; Myrffl/wt (3 m: N = 2, 6 m: N = 4). Data shown as mean ± SEM. Statistical significance determined by two-way ANOVA with Tukey’s multiple comparisons test. i Quantification of mbp:nls+ OLs in the zebrafish dorsal spinal cord of each genotype. WT (N = 5), myrfue70/WT (N = 9), fbxw7vo86/WT (N = 6), fbxw7vo86/vo86 (N = 6), fbxw7vo86/vo86; myrfue70/WT (N = 4). Mean ± SEM, statistical significance determined by two-way ANOVA with Tukey’s multiple comparisons test.
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