Fig. 4

Case-derived oligodendrocytes are morphologically impaired in vitro and, in a mouse-model recapitulating the translocation. a O4 staining of week 3 oligodendrocytes shows decreased cellular size and complexity of case-derived cells. b Quantification of cellular area showing the effect of t(1;11) translocation among different case-derived oligodendrocytes. n = 95 for control (three lines) and 120 for case (4 lines) oligodendrocytes. Mean ± SEM shown with paired t-test used for assessing statistical significance (p-value < 0.01). c Case oligodendrocytes have simpler morphology with fewer branch points away from the cell soma as assessed by Sholl analysis. Mean values shown and unpaired t-test used to assess statistical significance (p-value < 0.001). d Low magnification image of myelin basic protein (MBP) staining in the P21 Der1/+ cortex shows absence of gross cortical abnormalities. (Ctx cerebral cortex, Str striatum, CC corpus callosum). e Reconstructions of myelinated segments of upper cortical layer neurons from boxed region in a of wild-type (+/+) and Der1 heterozygous (Der1/+) brains stained for MBP and paranodal protein Caspr. Arrowheads demarcate myelin segments used for quantification. f Graph showing internodal length measurements from b. Each data point represents one myelin segment and the graph contains pooled data from n ≥ 50 segments each from three animals per genotype. p < 0.05 Unpaired t-test with Welch’s correction. g–i Electron microscopy analysis of the corpus callosum of wild-type and Der1/+mice (g) shows that thickness of myelin (h) and the relative frequency of myelinated fibers (i) are not affected due to the translocation. More than 250 axons measured in each group from 4 animals per genotype. j–l Single-oligodendrocyte analysis using by CNPase staining j at P42 supports findings in e, f and shows an increase in number of processes per oligodendrocytes (k) but a decrease in internodal length (l). Each data points represents one cell and the graph contains pooled data from n = 28 cells each from 4 animals per genotype. p < 0.05 Unpaired t-test. Scale bars: a 20 μm, d 500 μm, e 10 μm, g 1 µm, j 20 µm