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Translational Neuroscience

, Volume 1, Issue 3, pp 214–227 | Cite as

C. elegans models of neuromuscular diseases expedite translational research

  • James N. Sleigh
  • David B. SattelleEmail author
Review Article
  • 101 Downloads

Abstract

The nematode Caenorhabditis elegans is a genetic model organism and the only animal with a complete nervous system wiring diagram. With only 302 neurons and 95 striated muscle cells, a rich array of mutants with defective locomotion and the facility for individual targeted gene knockdown by RNA interference, it lends itself to the exploration of gene function at nerve muscle junctions. With approximately 60% of human disease genes having a C. elegans homologue, there is growing interest in the deployment of lowcost, high-throughput, drug screens of nematode transgenic and mutant strains mimicking aspects of the pathology of devastating human neuromuscular disorders. Here we explore the contributions already made by C. elegans to our understanding of muscular dystrophies (Duchenne and Becker), spinal muscular atrophy, amyotrophic lateral sclerosis, Friedreich’s ataxia, inclusion body myositis and the prospects for contributions to other neuromuscular disorders. A bottleneck to low-cost, in vivo, large-scale chemical library screening for new candidate therapies has been rapid, automated, behavioural phenotyping. Recent progress in quantifying simple swimming (thrashing) movements is making such screening possible and is expediting the translation of drug candidates towards the clinic.

Keywords

Caenorhabditis elegans Neuromuscular disease Drug screening Duchenne muscular dystrophy Spinal muscular atrophy Amyotrophic lateral sclerosis 

Abbreviations

AD

Alzheimer’s disease

ALS

amyotrophic lateral sclerosis

APP

amyloid precursor protein

Aβ

amyloid-β peptide

BMD

Becker muscular dystrophy

DMD

Duchenne muscular dystrophy

DPC/DAPC

dystrophin-associated protein complex

FALS

familial ALS

FRDA

Friedreich’s ataxia

FTX

frataxin

GABA

gamma-aminobutyric acid

GFP

green fluorescent protein

IBM

inclusion body myositis

RNAi

RNA interference

RRM

RNA-recognition motif

SMA

spinal muscular atrophy

SMN

survival motor neuron

SOD

superoxide dismutase

TDP/TARDBP

TAR DNA-binding protein

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© © Versita Warsaw and Springer-Verlag Wien 2010

Authors and Affiliations

  1. 1.MRC Functional Genomics Unit, Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
  2. 2.Faculty of Life SciencesUniversity of ManchesterManchesterUK

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