Myotonia congenita-associated mutations in chloride channel-1 affect zebrafish body wave swimming kinematics

PLoS One. 2014 Aug 1;9(8):e103445. doi: 10.1371/journal.pone.0103445. eCollection 2014.

Abstract

Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1). Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in human patients suffering from myotonia congenita. We developed video analytic tools that are able to provide precise quantitative measurements of movement abnormalities in order to analyse the effect of these CLCN1 mutations on adult transgenic zebrafish swimming. Two new parameters for body-wave kinematics of swimming reveal changes in body curvature and tail offset in transgenic zebrafish expressing the disease-associated CLCN1 mutants, presumably due to their effect on muscle function. The capability of the developed video analytic tool to distinguish wild-type from transgenic zebrafish could provide a useful asset to screen for compounds that reverse the disease phenotype, and may be applicable to other movement disorders besides myotonia congenita.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Animals
  • Animals, Genetically Modified
  • Biomechanical Phenomena
  • Chloride Channels / genetics*
  • Disease Models, Animal
  • Gene Expression
  • Gene Order
  • Genetic Vectors / genetics
  • Humans
  • Locomotion / genetics
  • Muscles / metabolism
  • Mutation*
  • Myotonia Congenita / diagnosis
  • Myotonia Congenita / genetics*
  • Phenotype
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Swimming*
  • Zebrafish / genetics*

Substances

  • Actins
  • CLC-1 channel
  • Chloride Channels
  • Recombinant Fusion Proteins

Grants and funding

This work was funded by grants 10/03/EG/05/02 and 1031C004 from the Joint Council Office of the Agency for Science Technology and Research (A*STAR), Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.