期刊
SCIENCE
卷 320, 期 5875, 页码 524-527出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1155085
关键词
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资金
- NICHD NIH HHS [P30 HD024064, R01 HD055835, HD055835, P30 HD001799] Funding Source: Medline
- NINDS NIH HHS [P30 NS055077, R01NS50414, R01 NS050414] Funding Source: Medline
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.
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