Autosomal recessive childhood onset spinal muscular atrophy (SMA) is a lead
ing cause of infant mortality caused by mutations in the survival motor neu
ron (SMN) gene, The SMN protein is involved in RNA processing and is locali
sed in structures called GEMs in the nucleus, Nothing is yet understood abo
ut why mutations in SMN gene result in the selective motor neuron loss obse
rved in patients, The SMN protein domains conserved across several species
may indicate functionally significant regions, Exon 3 of SMN contains homol
ogy to a tudor domain, where a Type I SMA patient has been reported to harb
our a missense mutation, We have generated missense mutants in this region
of SMN and have tested their ability to form GEMs when transfected into HeL
a cells, Our results show such mutant SMN proteins still localise to GEMs,
Furthermore, exon 7 deleted SMN protein appears to exert a dominant negativ
e effect on localisation of endogenous SMN protein, However, exon 3 mutant
protein and exon 5 deleted protein exert no such effect.