%0 Journal Article %A Ashlyn M. Spring %A Amanda C. Raimer %A Christine D. Hamilton %A Michela J. Schillinger %A A. Gregory Matera %T Comprehensive modeling of Spinal Muscular Atrophy in Drosophila melanogaster %D 2018 %R 10.1101/394908 %J bioRxiv %P 394908 %X Spinal muscular atrophy (SMA) is a common neurodegenerative disorder that affects motor neurons, primarily in young children. SMA is caused by loss-of-function mutations in the Survival Motor Neuron 1 (SMN1) gene and a corresponding reduction in SMN protein levels. SMN functions in the assembly of spliceosomal RNPs and is well conserved in many model systems including mouse, zebrafish, fruitfly, nematode, and fission yeast. Work in Drosophila melanogaster has focused on molecular and cellular functions of SMN, primarily using null alleles or strong hypomorphs. A systematic analysis of SMA-related phenotypes over a range of Smn alleles has not been performed in the fly. This has led to debate over the validity of Drosophila as a proper model for SMA. We therefore examined fourteen fly lines expressing single SMA patient-derived SMN missense mutations for defects in both the larval and adult stages. Animals were evaluated on the basis of organismal viability and longevity, locomotor function, neuromuscular junction structure and development, muscle health, and immune system function. In all cases, we observed phenotypes consistent with those found in human SMA patients. Severity of these defects is variable, and forms a broad spectrum across the fourteen lines examined. We assert that these fly lines constitute an effective model for SMA, recapitulating the full range of phenotypic severity observed in human SMA patients. %U https://www.biorxiv.org/content/biorxiv/early/2018/09/21/394908.full.pdf