Spinal muscular atrophy (SMA) is a common human neuromuscular disorder characterised by a progressive degeneration of the spinal motor neurons and inherited in an autosomal, recessive manner. The causative gene has been termed SMN (Survival of Motor Neurons), with orthologues described in a number of species including C. elegans (
smn-1 on C41G7.1) (1). The SMN protein functions in the assembly of ribonucleoproteins involved in RNA splicing, ribosomal biogenesis and may also be involved in transcriptional regulation. In spite of its housekeeping function it is unclear why motorneurons are especially susceptible to loss of SMN. SPF30 (or SMN-related protein) is a paralogue of SMN and is an essential splicing factor involved in the formation of the spliceosome (2). Its C. elegans orthologue is Y77D11A.2. We have characterised the phenotype of
smn-1 (
ok355), a null allele we obtained from the C. elegans gene knockout consortium. Homozygous worms carrying the mutation arrest at the L3 stage displaying reduced pharyngeal pumping, defecation rate and movement, all of which progressively worsen leading to paralysis and death. We are currently analysing the organisation of the nervous system in the
smn-1(
ok355) mutants using the pan-neuronal: :gfp marker (NW1229). In addition, we have cloned the Y77D11A.2 cDNA and have carried out RNAi on both N2 and
rrf-3 (
pk1426) strains. We find embryonic lethality, developmental delay with larvae forming a protrusion in the middle of the animal with all the defects being especially pronounced in
rrf-3 background. Y77D11A.2::GFP expression is present throughout development and is particularly strong in adult body wall muscle, pharynx and nerve cord. We are interested in investigating a possible functional link between
smn-1 and Y77D11A.2 in the worm. RNAi of Y77D11A.2 does not cause further deterioration of
smn-1 worms (on an N2 background) so we are currently examining the effects of overexpressing it in the
smn-1(
ok355) mutant. 1.Miguel-Aliaga I. et al (1999). Hum Mol Genet. 8: 2133-43; 2.Talbot K. et al (1998). Hum Mol Genet. 7: 2149-56