ZFIN ID: ZDB-PUB-060908-1
The use of zebrafish mutants to identify secondary target effects of acetylcholine esterase inhibitors
Behra, M., Etard, C., Cousin, X., and Strähle, U.
Date: 2004
Source: Toxicological sciences : an official journal of the Society of Toxicology   77(2): 325-333 (Journal)
Registered Authors: Behra, Martine, Cousin, Xavier, Etard, Christelle, Strähle, Uwe
Keywords: zebrafish, acetylcholinesterase, inhibitors, animal model, secondary drug targets
MeSH Terms:
  • Acetylcholinesterase/analysis
  • Acetylcholinesterase/genetics
  • Animals
  • Animals, Genetically Modified*
  • Cholinesterase Inhibitors/toxicity*
  • Embryo, Nonmammalian/drug effects*
  • Gene Transfer Techniques
  • Models, Animal
  • Motor Activity/drug effects
  • Toxicity Tests/economics
  • Toxicity Tests/methods
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
PubMed: 14657522 Full text @ Toxicol. Sci.
ABSTRACT
We are confronted with a large and steadily growing number of bioactive compounds, including drugs, pesticides, and industrial by-products. The assessment of target specificity and potential toxic effect on human health and the environment generates a strong demand for robust and cost-effective models with high predictive power. We investigated the potential of the zebrafish embryo as a whole organism, vertebrate model to assess the specificity of compounds that are known to inhibit acetylcholinesterase (AChE). Inhibitors of AChE are widely used as drugs and pesticides. By application of simple assays and comparison with the phenotype of embryos with genetic lesions in the ache gene, we demonstrate that only one of the AChE inhibitors (galanthamine) reproduces the phenotype of ache mutant embryos. The other compounds produced additional effects indicating secondary targets. Our work demonstrates the power of a genetic system for toxicological evaluations. The combination of genetics and transgenesis with the other experimental virtues of the zebrafish embryo, such as small size and low cost, offers a whole organism platform for medium to high throughput compound testing.
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