Gene expression profiling of vulnerable spinal motor neurons in the SMNΔ7 mouse model of SMA upon modulation of p53 signaling

However, the downstream transcriptional programs that execute motor neuron death remain incompletely defined.To characterize p53-associated transcriptional changes in vulnerable motor neurons, we performed RNA sequencing of cholera toxin subunit B (CTB)-labeled lumbar (L1–L3) motor neurons isolated by laser-capture microdissection from postnatal day 6 SMNΔ7 (SMNΔ7;SMN2;Smn−/−) SMA mice and wild-type littermate controls.

Disease-associated gene expression changes were defined by comparison of SMA and wild-type motor neurons. To assess pathway-specific contributions, untreated SMA mice were compared to SMA mice treated with Pifithrin-α (inhibitor of p53 transcriptional activity), MW150 (p38 MAPK inhibitor that prevents p53 phosphorylation), or SMN-C3 (SMN splicing modifier). Differential gene expression analysis was performed using kallisto-based transcript quantification and DESeq2.