A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle

作者：Rajendra T K; Gonsalvez Graydon B; Walker Michael P; Shpargel Karl B; Salz Helen K; Matera A Gregory^*

来源：The Journal of Cell Biology, 2007, 176(6): 831-841.

DOI：10.1083/jcb.200610053

Mutations in human survival motor neurons 1 (SMN1) cause spinal muscular atrophy (SMA) and are associated with defects in assembly of small nuclear ribonucleoproteins (snRNPs) in vitro. However, the etiological link between snRNPs and SMA is unclear. We have developed a Drosophila melanogaster system to model SMA in vivo. Larval-lethal Smn-null mutations show no detectable snRNP reduction, making it unlikely that these animals die from global snRNP deprivation. Hypomorphic mutations in Smn reduce dSMN protein levels in the adult thorax, causing flightlessness and acute muscular atrophy. Mutant flight muscle motoneurons display pronounced axon routing and arborization defects. Moreover, Smn mutant myofibers fail to form thin. laments and phenocopy null mutations in Act88F, which is the flight muscle-specific actin isoform. In wildtype muscles, dSMN colocalizes with sarcomeric actin and forms a complex with alpha-actinin, the thin. lament crosslinker. The sarcomeric localization of Smn is conserved in mouse myofibrils. These observations suggest a muscle-specific function for SMN and underline the importance of this tissue in modulating SMA severity.

• 出版日期2007-3