Distinct expression profiles in mice with oligodendroglial TDP-43 deletion. (A) Graphic summary of phenotypes and symptoms of oligodendroglial TDP-43 deletion mice. Oligodendroglial TDP-43 mice showed progressive demyelination phenotypes. Spinal cords from P21 and P60 mice were used for RNA-seq analysis. (B) Black-Gold staining of myelin tracks in the lumbar spinal cords of Tardbp^fl/fl, Cnp-Cre;Tardbp^fl/+, and Cnp-Cre⁺;Tardbp^fl/fl mice. RNAs from the whole spinal cords of Tardbp^fl/fl, Cnp-Cre;Tardbp^fl/+, and Cnp-Cre⁺;Tardbp^fl/fl mice from P21 and P60 time points were subjected to RNA-seq analyses. n = 4 per genotypes for P21, n = 3 per genotypes for P60. (C) PCA of count data across all three conditions shows a clear separation of Cnp-Cre⁺;Tardbp^fl/fl samples from Tardbp^fl/fl and Cnp-Cre;Tardbp^fl/+ samples across the first two principal components. (D) Hierarchical clustering of gene-centered count data cleanly categorizes the data, clustering Cnp-Cre⁺;Tardbp^fl/fl samples separately from both Tardbp^fl/fl and Cnp-Cre;Tardbp^fl/+ samples. (E) Normalized expression information for myelin-related and knockout-related genes from P60 mice. Error bars describe expression SD, and Wald testing was done for significance. *, FDR-corrected P < 0.05. (F) Top six GO terms (Biological Process) for down-regulated and up-regulated genes show a clear split in function. A two-sided hypergeometric test was performed for significance, and the -log10(Bonferroni-corrected P values) are presented. (G) Reactome pathway projection of a selected GO term cluster reveals a marked dysregulation of cholesterol biosynthetic pathways. Statistical significance of the enrichment was tested using a two-sided hypergeometric test, and -log10(FDR-corrected P values) are reported along with mean log2(fold change) of genes in the pathways.