PUBLICATION

An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos

Authors
Jarque, S., Fetter, E., Veneman, W.J., Spaink, H.P., Peravali, R., Strähle, U., Scholz, S.
ID
ZDB-PUB-180830-10
Date
2018
Source
PLoS One   13: e0203087 (Journal)
Registered Authors
Peravali, Ravindra, Spaink, Herman P., Strähle, Uwe
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Antithyroid Agents/pharmacology*
  • Automation, Laboratory*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical/methods*
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Image Processing, Computer-Assisted
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Microscopy, Fluorescence
  • Thyroid Gland/drug effects
  • Thyroid Gland/metabolism
  • Zebrafish
PubMed
30157258 Full text @ PLoS One
CTD
30157258
Abstract
The knowledge on environmentally relevant chemicals that may interfere with thyroid signaling is scarce. Here, we present a method for the screening of goitrogens, compounds that disrupt the thyroid gland function, based on the automatic orientation of zebrafish in a glass capillary and a subsequent imaging of reporter gene fluorescence in the thyroid gland of embryos of the transgenic zebrafish line tg(tg:mCherry). The tg(tg:mCherry) reporter gene indicates a compensatory upregulation of thyroglobulin, the thyroid hormone precursor, in response to inhibition of thyroid hormone synthesis. Fish embryos were exposed to a negative control compound (3,4-dichloroaniline), or a concentration series of known goitrogenic compounds (resorcinol, methimazole, potassium perchlorate, 6-propyl-2-thiouracil, ethylenethiourea, phloroglucinol, pyrazole) with maximum exposure concentration selected based on mortality and/or solubility. Exposure to 3,4-dichloroaniline decreased the fluorescence signal. All goitrogenic compounds exhibited clear concentration-dependent inductions of reporter fluorescence 1.4 to 2.6 fold above control levels. Concentration-response modelling was used to calculate goitrogenic potencies based on EC50 values. The new automated method offers an efficient screening approach for goitrogenic activity.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping