Figure 7. ALS patient spinal cord motor neurons have decreased expression of STMN2 and express transcripts containing the cryptic exon.

(a-c) Histologic analysis of human adult lumbar spinal cord from post-mortem samples collected from a subject with no evidence of spinal cord disease (control) (a) or two patients diagnosed with sporadic ALS (b-c). The experiment was performed with n= 3 controls and 3 ALS cases. STMN2 immunoreactivity in lumbar spinal motor neurons from control and ALS cases was scored as ‘strong’ or as ‘absent’. Scale bars, 50 μm. (d) The percentage of lumbar spinal motor neurons with strong STMN2 immunoreactivity was significantly lower in ALS tissue samples. Data are displayed as the mean with SD for n= 3 controls and 3 ALS cases; approximately 40 MNs were scored for each subject (Unpaired t-test, two-sided, P value < 0.05). (e-g) Meta-analysis of STMN2 transcript abundance in previously published data sets for laser captured lumbar motor neurons analyzed by microarray n= 10 controls and 12 ALS cases displayed (Rabin et al 2009, e), laser captured lower motor neurons analyzed by microarray n= 6 controls and 6 ALS cases (Highley et al 2014, f), individuals are displayed as dots with mean and SD (moderated t-test, P value < 0.05, (e-f)), and spinal cord ventral horns analyzed by RNA-Seq for n= 8 controls and 9 ALS cases, individuals are displayed as dots with mean (D’Erchia et al 2017, Wald test and a cutoff of 0.1 for Benjamini-Hochberg adjusted p values with no log2 fold-change ratio cutoff, (g)). (h-i) Visualization of the cryptic exon for STMN2 from the NINDS datasets (g) for the ventral horns of controls (h) and sporadic ALS patient (i) spinal cords. Read coverage and splice junctions are shown for alignment of the samples to the human hg19 genome. Splice ribbons from exon 1 to the cryptic exon are highlighted in orange.