Chapter 14 - Nonmammalian Animal Models of Spinal Muscular Atrophy

Abstract

Nonmammalian models of spinal muscular atrophy (SMA) have furthered our understanding of how loss of survival of motor neuron (SMN) protein leads to motor neuron defects. Well-conserved orthologs of SMN exist in Drosophila, Caenorhabditis elegans, and zebrafish. Loss of function mutations in these orthologs provide SMA models that display common neuromuscular phenotypes suggesting conserved function across species. These SMA models allow researchers to conduct large-scale screens, investigate specific cells with invariant lineages, and compare effects of orthologous protein loss across species. They have also advanced our knowledge of the cell-autonomous roles of SMN and of the impact of SMN loss on motor neuron development. Genetic and drug screens in nonmammalian models have contributed to the dissection of molecular pathways downstream of SMN providing avenues for future therapeutic approaches. This chapter describes the power of these models, their contribution to the SMA field, and their future potential for understanding SMA.