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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Minimal expression of dysferlin prevents development of dysferlinopathy in dysferlin exon 40a knockout mice

Fig. 3

Proteomics analysis of Dysferlin Exon 40a knockout mice. Quadriceps muscle sections from three dysf40a KO lines expressing variable amounts of dysferlin protein (KO-1low, KO-2mid and KO-3high, all aged 18 weeks) were subjected to LC–MS/MS for proteomics analysis alongside age-matched control WT and dysferlin-null BLAJ mice. Samples were probed across two different experiments, with the first set comprising KO-1, KO-2, WT and BLAJ (left side panels) and the second set comprising KO-3, KO-2, WT and BLAJ (right side panels), n = 4 samples/group. For each of the six categories of proteins listed in the figure, a principal component analysis (PCA) graph has been plotted with the corresponding heatmap expression panel displayed directly below it, to highlight differences and similarities between groups. a, b PCA plot of all proteins analysed shows that KO lines have a similar overall proteomic profile that is distinct from that of WT and BLAJ, which constitute the greatest phenotypic differences. (C, D) Heatmap of the top 100 altered proteins showed similar trends to the PCA plots in (a) and (b). e–h PCA and heatmap analysis of common dysferlin-associated proteins shows vast differences between WT and BLAJ and a dysferlin-dose dependent effect on expression of these proteins in KO lines. i–l Analysis of lipid metabolism proteins also showed a dysferlin-dose dependent effect, KO1low clustered with BLAJ, KO2mid showed partial segregation from BLAJ while KO-3high was well segregated from BLAJ. m–p Expression patterns of mitochondrial and oxidative proteins were similar to lipid metabolism proteins except, KO lines were more similar to WT than BLAJ. q–t Expression of contractile and structural proteins mirrored the expression pattern of dysferlin-associated proteins (e–h). u–x Analysis of ECM proteins showed minimal segregation (differences) between WT, BLAJ and KO lines. ANOVA post-hoc statistical analysis for each of the heatmap expression panels can be found in Supplementary Tables 3–7. For all heatmap data displayed, conventional protein/gene abbreviations have been used which can be searched in online protein databases or in Supplementary Table 2 for reference

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