Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy
Graduate School of Biomedical Sciences; Institute of Human Genetics; Department of Cell Biology
Life Sciences | Medicine and Health Sciences
Homozygous deletion of the survival motor neuron 1 gene (SMN1) causes spinal muscular atrophy (SMA), the most frequent genetic cause of early childhood lethality. In rare instances, however, individuals are asymptomatic despite carrying the same SMN1 mutations as their affected siblings, thereby suggesting the influence of modifier genes. We discovered that unaffected SMN1-deleted females exhibit significantly higher expression of plastin 3 (PLS3) than their SMA-affected counterparts. We demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish. Our study suggests that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.
DOI of Published Version
Science. 2008 Apr 25;320(5875):524-7. Link to article on publisher's site
Science (New York, N.Y.)
Oprea GE, Krober S, McWhorter ML, Rossoll W, Muller S, Krawczak M, Bassell GJ, Beattie CE, Wirth B. (2008). Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. GSBS Student Publications. https://doi.org/10.1126/science.1155085. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1492