title: Zebrafish biosensor for toxicant induced muscle hyperactivity.
abstract: Robust and sensitive detection systems are a crucial asset for risk management of chemicals, which are produced in increasing number and diversity. To establish an in vivo biosensor system with quantitative readout for potential toxicant effects on motor function, we generated a transgenic zebrafish line TgBAC(hspb11:GFP) which expresses a GFP reporter under the control of regulatory elements of the small heat shock protein hspb11. Spatiotemporal hspb11 transgene expression in the musculature and the notochord matched closely that of endogenous hspb11 expression. Exposure to substances that interfere with motor function induced a dose-dependent increase of GFP intensity beginning at sub-micromolar concentrations, while washout of the chemicals reduced the level of hspb11 transgene expression. Simultaneously, these toxicants induced muscle hyperactivity with increased calcium spike height and frequency. The hspb11 transgene up-regulation induced by either chemicals or heat shock was eliminated after co-application of the anaesthetic MS-222. TgBAC(hspb11:GFP) zebrafish embryos provide a quantitative measure of muscle hyperactivity and represent a robust whole organism system for detecting chemicals that affect motor function.
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.|Faculty of Biosciences, Ruprecht-Karls-University of Heidelberg, D69120 Heidelberg, Germany.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.
authors.forename: Masanari
authors.initials: M
authors.lastname: Takamiya
authors.affiliation: Institute for Applied Computer Sciences, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stegmaier
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.|Faculty of Biosciences, Ruprecht-Karls-University of Heidelberg, D69120 Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Middel
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.
authors.forename: Marion
authors.initials: M
authors.lastname: Gradl
authors.affiliation: Department of Bioanalytical Ecotoxicology, UFZ - Helmholtz Centre for Environmental Research, D04318 Leipzig, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Klüver
authors.affiliation: Institute for Applied Computer Sciences, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Mikut
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dickmeis
authors.affiliation: Department of Bioanalytical Ecotoxicology, UFZ - Helmholtz Centre for Environmental Research, D04318 Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.
authors.forename: Sepand
authors.initials: S
authors.lastname: Rastegar
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.|Department of Environmental Pollution and Health, State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, 100012, Beijing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, D76021 Karlsruhe.|Faculty of Biosciences, Ruprecht-Karls-University of Heidelberg, D69120 Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001387:Azinphosmethyl / Q000032:analysis / Q000633:toxicity; D015374:Biosensing Techniques / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D018703:Founder Effect; D005702:Galantamine / Q000032:analysis / Q000633:toxicity; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D050506:Mutant Chimeric Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009672:Notochord / Q000187:drug effects / Q000378:metabolism; D010575:Pesticides / Q000032:analysis / Q000633:toxicity; D011401:Promoter Regions, Genetic; D001074:Propoxur / Q000032:analysis / Q000633:toxicity; D015027:Zebrafish
chemical_list: C525841:HSPB11 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050506:Mutant Chimeric Proteins; D010575:Pesticides; D005702:Galantamine; D049452:Green Fluorescent Proteins; D001387:Azinphosmethyl; D001074:Propoxur