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. 2018 Dec 4;29(1):23–41. doi: 10.1038/s41422-018-0113-8

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — Fto transgene triggers hypomyelination. a MeRIP-qPCR analysis of Olig2 RNA in m⁶A peak region in Fto transgenic (Tg) and wild-type (WT) mice at 4-weeks-old (two-tailed unpaired student’s t-test, ***P < 0.001, n = 4 per group). b Prrc2a RIP-qPCR analysis of Olig2 RNA in m⁶A peak region in Fto transgenic (Tg) and WT mice at 4 weeks old (two-tailed unpaired student’s t-test, **P < 0.01, n = 4 per group). c Cultured OPCs from WT and Fto transgenic mice were exposed to actinomycin D (1 μg/ml), then RNA was isolated at indicated time points. RT-qPCR was performed to assess the half-lives of Olig2 mRNA. The data were presented as means ± s.e.m. and the inserted numbers (T_{1/2 (WT)} = 73.3 ± 1.1 min; T_1/2(Tg) = 66.0 ± 0.6 min) show the calculated half-times from four independent experiments. d Volcano plot of RNA-seq data showing Fto-regulated genes from brain tissue samples of 4-week-old Fto transgenic vs. control mice. e Parts of GO terms of the biological process categories enriched in DEGs from Fto transgene vs. control samples. f Relative gene expression in hippocampus from 4-week-old Fto Tg and control mice (two-tailed unpaired student’s t-test, *P < 0.05, **P < 0.01, ***P < 0.001, n = 4 per group). g Immunostainings of Pdgfrα (P7), CC1/Olig2, or Sox10 (P28) in corpus callosum from mice with indicated genotypes. The quantification of Pdgfrα⁺, CC1⁺ Olig2⁺, and Sox10⁺ cells were shown in (h) (two-tailed unpaired student’s t-test, **P < 0.01, ***P < 0.001, Pdgfrα⁺: n = 6 each group; CC1⁺ Olig2⁺ cells: n = 5 per group, Sox10⁺ cells: n = 5 per group). i T2-weighted MRI of 4-week-old mice with indicated genotypes. j Black-gold staining of brain sections from 4-, 8-, and 32-week-old Fto Tg and control mice. k The quantification of corpus callosum width at the midline from 4-, 8-, and 32-week-old Fto Tg and control mice (two-tailed unpaired student’s t-test, *P < 0.05, **P < 0.01, 4w: n = 5 per group, 8w: n = 6 per group, 32w: n = 6 per group). l TEM analysis of the myelin fibers in the corpus callosum from mice with indicated genotypes and ages. The white arrowheads indicated the naked axons. m The percentage of myelinated axons in the corpus callosum from 4-, 8-, and 32-week-old mice with indicated genotypes (two-tailed unpaired student’s t-test, ***P < 0.001, 4w: n = 5 per group, 8w: n = 6 per group, 32w: n = 6 per group)