Additional file 8: Fig. S2. of Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation

Abstract

Transcript changes of Pink1-deficient mouse cerebellar tissue at the age of 18 months in qPCR analyses represented in bar graphs. (A) Significant downregulation of Srsf10 mRNA and upregulations of Creb3 and Nfkbia mRNAs confirm the alteration within spliceosomal, ER stress and neuroinflammation pathways. The significant dysregulation of a Ube3a splice isoform is particularly interesting as a potential target of the spliceosome alterations and in view of its role in the degradation of alpha-synuclein. The scheme of Ube3a exon intron structure with the location of different Taqman assays was adapted from the Thermo Fisher Scientific internet site. (B) Significant upregulations of Mapk8 mRNA at 3 different exon junctions, together with a scheme of the Mapk8 exon intron structure and the location of 3 different Taqman assays (modified from the Thermo Fisher Scientific internet site). Non-significant changes of the MAPK phosphorylation cascade components Mapk9 and Mapk14 mRNAs demonstrate the selectivity of transcriptional regulation. Significant upregulations in the downstream nuclear transcription regulators Creb3 and Nfkbia in the stress and inflammation response may reflect biological responses to the Mapk8 upregulation. The bar graphs show mean and standard error of the mean (10 Pink1 −/− versus 10 WT), illustrating the significance with asterisks (* p