Zebrafish as a neurotoxicological model
Zebrafish as a neurotoxicological model
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DOI：
10.1016/j.ntt.2004.06.015
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发表时间：
2004-11-01
影响因子：
2.9
通讯作者：
Donerly, S
中科院分区：
文献类型：
--
作者：
Linney, E;Upchurch, L;Donerly, S
在几个不同物种中发现了共同的调控途径，基因组学开始允许比较基因、它们在染色体上的排列方式以及它们是如何受到调控的时候，斑马鱼已经成为一种有价值的互补脊椎动物模型。对证明价值的一些特征进行了描述和说明。斑马鱼胚胎的荧光转基因品系被用于神经毒物的时间线研究。虽然基因敲除技术尚未为该模型开发，但反义吗啡方法允许敲除3天胚胎期的基因表达。这可以为那些对胚胎发育至关重要的基因提供突变基因的表型，也可以提供对基因表达的有限抑制，从而允许鱼类的后续发育。随着斑马鱼基因组测序的努力，微阵列技术现在正在为模型系统开发。这些资源和技术使人们能够用毒物挑战系统，并用部分或全部神经系统发出荧光的转基因胚胎查看毒物的直接影响。已经为生物体制定了行为和学习方案，以便可以测试早期暴露对成年鱼的影响。微阵列技术应该允许人们识别受神经毒物影响的特定基因和途径。在未来，这些方法应该为探索神经毒物的分子机制提供一个有效的方案。然后，这种互补的方法应该允许更有效地检查和测试哺乳动物模型中的机制。(C)2004 Elsevier Inc.保留所有权利。
At a time when common regulatory pathways are being identified in several different species and genomics is beginning to allow comparisons of genes, how they are arranged on chromosomes and how they are regulated, zebrafish has emerged as a valuable and complementary vertebrate model. Some of the characteristics that prove of value are described and illustrated. Fluorescent transgenic lines of zebrafish embryos are presented for time-line studies with neurotoxicants. While genetic knockout technology has yet to be developed for the model, the anti-sense, morpholino approach allows for knockdown of expression of genes for the 3 day, embryonic period. This can provide for phenocopies of mutant genes for those genes essential to embryonic development or it can provide for a limited inhibition of gene expression that allows subsequent development of the fish. With the zebrafish genomic sequencing effort, microarray technology is now developing for the model system. These resources and technologies allow one to challenge the system with toxicants, and to view the immediate effects of the toxicants with transgenic embryos that fluoresce in part or all of the nervous system. Behavioral and learning protocols have been developed for the organism so that early exposures can be assayed for effects upon adult fish. Microarray technology should allow for one to identify specific genes and pathways affected by a neurotoxicant. In the future, these approaches should provide a working protocol for exploring molecular mechanisms of neurotoxicants. This type of complementary approach should then allow for more efficient examination and testing of mechanisms in mammalian models. (C) 2004 Elsevier Inc. All rights reserved.