Genetic suppression of phenotypes arising from mutations in dystrophin-related genes in Caenorhabditis elegans

Curr Biol. 2000 Sep 21;10(18):1092-7. doi: 10.1016/s0960-9822(00)00691-6.


Background: Dystrophin is the product of the gene that is mutated in Duchenne muscular dystrophy (DMD), a progressive neuromuscular disease for which no treatment is available. Mice carrying a mutation in the gene for dystrophin (mdx mice) display only a mild phenotype, but it is aggravated when combined with a mutation in the MyoD gene. The nematode worm Caenorhabditis elegans has a dystrophin homologue (dys-1), but null mutations in dys-1 do not result in muscle degeneration.

Results: We generated worms carrying both the dys-1 null mutation cx18, and a weak mutation, cc561ts, of the C. elegans MyoD homologue hlh-1. The double mutants displayed a time-dependent impairment of locomotion and egg laying, a phenotype not seen in the single mutants, and extensive muscle degeneration. This result allowed us to look for genes that, when misexpressed, could suppress the dys-1; hlh-1 phenotype. When overexpressed, the dyc-1 gene - whose loss-of-function phenotype resembles that of dys-1 - partially suppressed the dys-1; hlh-1 phenotype. The dyc-1 gene encodes a novel protein sharing similarities with the mammalian neural nitric oxide synthase (nNOS)-binding protein CAPON, and is expressed in the muscles of the worm.

Conclusions: As a C. elegans model for dystrophin-dependent myopathy, the dys-1; hlh-1 worms should permit the identification of genes, and ultimately drugs, that would reverse the muscle degeneration in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / anatomy & histology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Disease Models, Animal
  • Dystrophin / genetics*
  • Dystrophin / physiology
  • Genes, Reporter
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics*
  • Helminth Proteins / physiology
  • Mice
  • Molecular Sequence Data
  • Muscle Proteins
  • Muscles / pathology*
  • Muscular Dystrophy, Animal / genetics
  • Muscular Dystrophy, Animal / pathology
  • Mutagenesis
  • Myogenic Regulatory Factors
  • Nuclear Proteins
  • Phalloidine / pharmacology
  • Phenotype
  • Rats
  • Sequence Alignment
  • Suppression, Genetic*
  • Time Factors
  • Transcription Factors / genetics*
  • Transcription Factors / physiology


  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Dystrophin
  • Helminth Proteins
  • Muscle Proteins
  • Myogenic Regulatory Factors
  • NOS1AP protein, rat
  • Nos1ap protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • dys-1 protein, C elegans
  • HLH-1 protein, C elegans
  • Phalloidine