PUBLICATION
Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy
- Authors
- Oprea, G.E., Kröber, S., McWhorter, M.L., Rossoll, W., Müller, S., Krawczak, M., Bassell, G.J., Beattie, C.E., and Wirth, B.
- ID
- ZDB-PUB-080429-13
- Date
- 2008
- Source
- Science (New York, N.Y.) 320(5875): 524-527 (Journal)
- Registered Authors
- Beattie, Christine, McWhorter, Michelle
- Keywords
- none
- MeSH Terms
-
- SMN Complex Proteins
- Zebrafish/embryology
- Zebrafish/genetics
- Cyclic AMP Response Element-Binding Protein/genetics
- Cyclic AMP Response Element-Binding Protein/metabolism
- Pedigree
- Animals
- Cell Differentiation
- Spinal Cord/metabolism
- Growth Cones/metabolism
- Growth Cones/ultrastructure
- Membrane Glycoproteins
- Male
- Microfilament Proteins
- Female
- Humans
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism
- Cell Line
- Mice
- Actins/blood
- Actins/genetics*
- Actins/metabolism*
- Phosphoproteins/blood
- Phosphoproteins/genetics*
- Phosphoproteins/metabolism*
- Survival of Motor Neuron 1 Protein
- Muscular Atrophy, Spinal/genetics*
- Transcription, Genetic
- Gene Expression
- Axons/metabolism
- Axons/physiology*
- Axons/ultrastructure
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- PubMed
- 18440926 Full text @ Science
Citation
Oprea, G.E., Kröber, S., McWhorter, M.L., Rossoll, W., Müller, S., Krawczak, M., Bassell, G.J., Beattie, C.E., and Wirth, B. (2008) Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science (New York, N.Y.). 320(5875):524-527.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping