Transcriptional profiling of differentially vulnerable motor neurons at pre-symptomatic stage in the Smn 2b/- mouse model of spinal muscular atrophy

摘要: The term motor neuron disease encompasses a spectrum of disorders in which neurons are the lost. Importantly, while some lost early and others remain intact at end-stage. This creates valuable experimental paradigm to investigate factors that regulate vulnerability. Spinal muscular atrophy is childhood caused by mutations or deletions SMN1 gene. Here, we have performed transcriptional analysis on differentially vulnerable from an intermediate mouse model presymptomatic time point. We characterised two populations, differing level neuromuscular junction loss. Transcriptional cell bodies revealed reduced Smn levels correlate with reduction transcripts associated ribosome, rRNA binding, ubiquitination oxidative phosphorylation. Furthermore, P53 pathway activation precedes loss, suggesting denervation may be consequence, rather than cause death atrophy. Finally, increased vulnerability correlates decrease positive regulation DNA repair. study identifies pathways related function differential unit vulnerability, thus presenting number exciting targets for future therapeutic development.