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. 2018 Jul 28;14(8):1398–1403. doi: 10.1080/15548627.2018.1474311

Figure 1.

Figure 1.

The abundance of TARDBP regulated cryptic exons in ATG4B mRNA is an ALS tissue biomarker and TARDBP knockdown leads to down regulation of ATG4B. (a) Values of ATG4B mRNA analyses (± standard error) indicate that ATG4B cryptic exon levels are higher in samples from ALS when compared with controls. (b) RT-qPCR of ATG4B cryptic exons show different expression levels in spinal cord, frontal cortex, occipital cortex, and brain stem; ATG4B aberrant mRNA levels depend on ALS type (bulbar vs non-bulbar cases). (c) ATG4B cryptic exon levels in brainstem of ALS patients have a positive correlation with age and (d) a negative correlation with disease duration. Further, TARDBP knockdown (KD) in human neural tissue cells differentiated from iPSC induced significant increase of the amount of ATG4B cryptic exon levels, as quantified by RT-qPCR (e), with a downregulation of ATG4B protein (f) evaluated by western blot and quantified by densitometry. Bars indicate mean values with standard error. For (g) *** p < 0.001 for disease type in a 2-way ANOVA accounting for disease type and region. In (e) and (f)**** p < 0.0001 and ** p < 0.001 after Student’s t test (e) or post hoc Bonferroni analyses (f). AUC, area under the curve.