title: Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular atrophy gene, results in locomotor dysfunction and reduced lifespan.
abstract: Spinal muscular atrophy is the most common genetic cause of infant mortality and is characterized by degeneration of lower motor neurons leading to muscle wasting. The causative gene has been identified as survival motor neuron (SMN). The invertebrate model organism Caenorhabditis elegans contains smn-1, the ortholog of human SMN. Caenorhabditis elegans smn-1 is expressed in various tissues including the nervous system and body wall muscle, and knockdown of smn-1 by RNA interference is embryonic lethal. Here we show that the smn-1(ok355) deletion, which removes most of smn-1 including the translation start site, produces a pleiotropic phenotype including late larval arrest, reduced lifespan, sterility as well as impaired locomotion and pharyngeal activity. Mutant nematodes develop to late larval stages due to maternal contribution of the smn-1 gene product that allows to study SMN-1 functions beyond embryogenesis. Neuronal, but not muscle-directed, expression of smn-1 partially rescues the smn-1(ok355) phenotype. Thus, the deletion mutant smn-1(ok355) provides a useful platform for functional analysis of an invertebrate ortholog of the human SMN protein.
authors.affiliation: MRC Functional Genomics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Briese
authors.forename: Behrooz
authors.initials: B
authors.lastname: Esmaeili
authors.forename: Sandrine
authors.initials: S
authors.lastname: Fraboulet
authors.forename: Emma C
authors.initials: EC
authors.lastname: Burt
authors.forename: Stefanos
authors.initials: S
authors.lastname: Christodoulou
authors.forename: Paula R
authors.initials: PR
authors.lastname: Towers
authors.forename: Kay E
authors.initials: KE
authors.lastname: Davies
authors.forename: David B
authors.initials: DB
authors.lastname: Sattelle
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D008136:Longevity; D009043:Motor Activity; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D055533:Survival of Motor Neuron 1 Protein