Institute of Toxicology and Genetics Forschungszentrum Karlsruhe Karlsruhe Institute of Technology 76021 Karlsruhe, Germany.
Toxicol Sci. 2010 Jun;115(2):379-90. doi: 10.1093/toxsci/kfq053. Epub 2010 Feb 24.
The objective of this study was to characterize the mechanisms of action of the model environmental toxicant methyl mercury (MeHg) in the zebrafish embryo. Zebrafish embryos were exposed to MeHg, and the effective concentration and window of exposure were determined in wild-type and fluorescent reporter transgenic zebrafish embryos. Genes were systematically assessed for altered expression in response to MeHg by in situ hybridization. MeHg impairs development of the fin fold and the tail fin primordium. Alterations in transgene expression were noted at 6 microg/l MeHg, making this shh:gfp line the most sensitive biosensor of MeHg exposure. The matrix metalloproteases mmp9 and mmp13 and eight other genes are induced in the embryonic tail in response to MeHg. Our data suggest that MeHg impairs tail development at least partially by activation of the tissue remodeling proteases Mmp9 and Mmp13.
本研究的目的是描述模型环境毒物甲基汞 (MeHg) 在斑马鱼胚胎中的作用机制。将斑马鱼胚胎暴露于 MeHg 中,并在野生型和荧光报告转基因斑马鱼胚胎中确定有效浓度和暴露窗口。通过原位杂交系统评估基因对 MeHg 反应的表达变化。MeHg 会损害鳍褶和尾鳍原基的发育。在 6μg/l MeHg 时观察到转基因表达的改变,使 shh:gfp 线成为最敏感的 MeHg 暴露生物传感器。基质金属蛋白酶 mmp9 和 mmp13 以及其他 8 个基因在胚胎尾部对 MeHg 做出反应而被诱导。我们的数据表明,MeHg 通过激活组织重塑蛋白酶 Mmp9 和 Mmp13 至少部分地损害尾巴的发育。