Fig. 5
Analysis of the impact of mRNA transcriptomes in neocortex of 3- or 12-month-old TDP-43 cKO mice. a(i), The numbers of the unchanged, up-regulated, down-regulated, and splicing-changed genes, respectively, in the neocortex of 3- or 12-month-old TDP-43 cKO mice in comparison to the Ctrls. Only gene expression changed with FPKM> 0.2 were considered in the analysis. The numbers in the parentheses are the numbers of the differentially expressed genes in the neocortex of TDP-43 cKO mice at both the ages of 3 months and 12 months in comparison to the Ctrls. (ii), Scatter plot showing log2 fold change of neocortex gene expression of 3-month-old (left panel) and 12-month-old (right panel) TDP-43 cKO mice and control mice, respectively. The red, blue, and gray dots indicate up-regulated (q < 0.05), down-regulated (q < 0.05), and non-significantly changed genes, respectively, in the neocortex of TDP-43 cKO mice. Each dot represents the mean value of data from analysis of triplicate neocortex sample sets. (iii), Scatter plot showing the correlation of log2 fold change of genes altered in the neocortex of TDP-43 cKO mice at 12 months (x axis) and 3 months (y axis) of age. The purple and blue dots indicate neocortex genes the expression levels of which are altered only in 3-month-old TDP-43 cKO mice (40 genes) and only in 12-month-old TDP-43 cKO mice (109 genes), respectively. The 12 neocortex genes deregulated in TDP-43 cKO mice at both ages are indicated by the red dots (12 genes). (iv), Heat map representation of the expression patterns of the 161 (40 + 109 + 12) genes de-regulated in the neocortex of TDP-43 cKO mice. The expression levels of up-regulated and down-regulated genes are highlighted with different red and blue colors, respectively, in the 2 columns, with the individual gene names indicated on the side of the columns. b, Cortical RNAs of TDP-43 cKO and Ctrl mice at the age of 3 months or 12 months were analyzed by Cufflink/MISO as described. The percentages (%) of the processing alternations, i.e. alternative uses of poly-A sites (“poly (A) extension”), extensions of conserved exons (“Exon extension”), inclusions of conserved exons (“Exon inclusion”), exclusion of conserved exons (“Exon exclusion”) and inclusion of cryptic exons (“Cryptic exon inclusion”), are shown