Spinal motor neuron loss occurs through a p53-and-p21-independent mechanism in the Smn
Document Type
Article
Publication Date
12-28-2020
Keywords
JMG
JAX Source
Exp Neurol 2020 Dec 28; 337:113587
Volume
337
First Page
113587
Last Page
113587
ISSN
1090-2430
PMID
33382987
DOI
https://doi.org/10.1016/j.expneurol.2020.113587
Abstract
Spinal muscular atrophy (SMA) is a pediatric neuromuscular disease caused by genetic deficiency of the survival motor neuron (SMN) protein. Pathological hallmarks of SMA are spinal motor neuron loss and skeletal muscle atrophy. The molecular mechanisms that elicit and drive preferential motor neuron degeneration and death in SMA remain unclear. Transcriptomic studies consistently report p53 pathway activation in motor neurons and spinal cord tissue of SMA mice. Recent work has identified p53 as an inducer of spinal motor neuron loss in severe Δ7 SMA mice. Additionally, the cyclin-dependent kinase inhibitor P21 (Cdkn1a), an inducer of cell cycle arrest and mediator of skeletal muscle atrophy, is consistently increased in motor neurons, spinal cords, and other tissues of various SMA models. p21 is a p53 transcriptional target but can be independently induced by cellular stressors. To ascertain whether p53 and p21 signaling pathways mediate spinal motor neuron death in milder SMA mice, and how they affect the overall SMA phenotype, we introduced Trp53 and P21 null alleles onto the Smn
Recommended Citation
Reedich E,
Kalski M,
Armijo N,
Cox GA,
DiDonato C.
Spinal motor neuron loss occurs through a p53-and-p21-independent mechanism in the Smn Exp Neurol 2020 Dec 28; 337:113587