title: Myotonia congenita-associated mutations in chloride channel-1 affect zebrafish body wave swimming kinematics.
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.
authors.affiliation: Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Institute for Infocomm Research, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Neurology and Deparment of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Burgunder
authors.affiliation: Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, Singapore; Department of Physiology, National University of Singapore, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
authors.affiliation: Institute for Infocomm Research, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: How-Lung
authors.initials: HL
authors.lastname: Eng
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001696:Biomechanical Phenomena; D018118:Chloride Channels / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008124:Locomotion / Q000235:genetics; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D009224:Myotonia Congenita / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013550:Swimming; D015027:Zebrafish / Q000235:genetics*
chemical_list: D000199:Actins; C086321:CLC-1 channel; D018118:Chloride Channels; D011993:Recombinant Fusion Proteins
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