Michael Briese1, Behrooz Esmaeili2, Laurence A. Brown1, Emma Burt1, Paula Towers1 and David B. Sattelle1. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder in which lower motor neurons in the spinal cord degenerate causing progressive muscle wasting. The predominant form of SMA shows childhood-onset and is associated with deletions or mutations of the Survival Motor Neuron 1 (SMN1) gene. Its C. elegans orthologue
smn-1 is expressed in neurons, muscles and other cells and knockdown of
smn-1 by RNA interference (RNAi) results in embryonic lethality and sterility. We have investigated the
smn-1(
ok355) deletion mutant which is sterile and arrests at larval stage L2-L3. Mutant worms show defects in pharyngeal pumping, movement and defecation. The movement defect becomes apparent at the late L1 stage in the form of an abnormal backward motion. As development proceeds, mutant animals become uncoordinated for both forward and backward movement. Using GFP reporters expressed pan-neuronally (F25B3.3::GFP) or in cholinergic neurons (
unc-17::GFP), we could not detect any gross morphological abnormalities of the nervous system architecture. We are currently in the process of scoring
smn-1(
ok355) worms for synaptic defects using synaptic markers, including
unc-25::SNB-1::GFP. We are also investigating the neuromuscular functions of SMN-1 in C. elegans by attempting to knock down
smn-1 through promoter-driven hairpin RNAi. To this end we are using the plasmid pWormgatePro which we have previously tested on genes expressed in muscle cells and neurons. Additionally, C. elegans embryonic cell cultures are being deployed to investigate cell-autonomous functions of
smn-1 in neurons and muscles.