Neurogenetics

, Volume 2, Issue 1, pp 61–72

Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to hyperactivity and suggest a link with cholinergic transmission

Authors

  • Catherine Bessou
    • IPMC, CNRS-UPR411, 660 route des Lucioles, F-06560 Sophia Antipolis, France Tel :+33 4 93 95 77 90; Fax: +33 4 93 95 77 08 e-mail: segalat@ipmc.cnrs.fr
  • Jean-Bernard Giugia
    • IPMC, CNRS-UPR411, 660 route des Lucioles, F-06560 Sophia Antipolis, France Tel :+33 4 93 95 77 90; Fax: +33 4 93 95 77 08 e-mail: segalat@ipmc.cnrs.fr
  • Christopher J. Franks
    • School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK
  • Lindy Holden-Dye
    • School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK
  • L. Ségalat
    • IPMC, CNRS-UPR411, 660 route des Lucioles, F-06560 Sophia Antipolis, France Tel :+33 4 93 95 77 90; Fax: +33 4 93 95 77 08 e-mail: segalat@ipmc.cnrs.fr
Original article

DOI: 10.1007/s100480050053

Cite this article as:
Bessou, C., Giugia, J., Franks, C. et al. Neurogenetics (1998) 2: 61. doi:10.1007/s100480050053

ABSTRACT

Mutations in the human dystrophin gene cause Duchenne muscular dystrophy, a common neuromuscular disease leading to a progressive necrosis of muscle cells. The etiology of this necrosis has not been clearly established, and the cellular function of the dystrophin protein is still unknown. We report here the identification of a dystrophin-like gene (named dys-1) in the nematode Caenorhabditis elegans. Loss-of-function mutations of the dys-1 gene make animals hyperactive and slightly hypercontracted. Surprisingly, the dys-1 mutants have apparently normal muscle cells. Based on reporter gene analysis and heterologous promoter expression, the site of action of the dys-1 gene seems to be in muscles. A chimeric transgene in which the C-terminal end of the protein has been replaced by the human dystrophin sequence is able to partly suppress the phenotype of the dys-1 mutants, showing that both proteins share some functional similarity. Finally, the dys-1 mutants are hypersensitive to acetylcholine and to the acetylcholinesterase inhibitor aldicarb, suggesting that dys-1 mutations affect cholinergic transmission. This study provides the first functional link between the dystrophin family of proteins and cholinergic transmission.

Key words Caenorhabditis elegansDystrophinDuchenne muscular dystrophyAcetylcholine
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Copyright information

© Springer-Verlag Berlin Heidelberg 1998