Zebrafish as a novel experimental model for developmental toxicology.
Zebrafish as a novel experimental model for developmental toxicology.
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DOI：
10.1111/j.1741-4520.2003.tb01036.x
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发表时间：
2003-06-01
影响因子：
1.3
通讯作者：
Hiraga, Takeo
中科院分区：
文献类型：
--
作者：
Teraoka, Hiroki;Dong, Wu;Hiraga, Takeo
人们普遍认为，发育中的胚胎和婴儿对化学物质高度敏感，这些化学物质会对生长造成严重损害。然而，关于发育毒性机制的知识很少。其中一个原因是有限的方便的模型系统，而不是使用啮齿动物的器官培养来研究发育毒理学的各个方面。培养的细胞并不总是足以达到这一目的，因为形态发生中的事件是通过与其他组织的相互作用来处理的。斑马鱼胚胎是发育生物学中最重要的生物之一。应用于果蝇和线虫以确定基因功能的饱和诱变已在斑马鱼中进行，但几乎没有其他脊椎动物，并且由于这种胚胎的快速生长和透明体，可获得数千个品系。基因组和EST的增强数据库可在具有丰富遗传和生物背景的网站上查阅。通过用吗啉修饰的反义寡核苷酸（吗啉代）敲低靶向基因，特定蛋白质的翻译可以被暂时阻断数天。许多报告系统在体内已经建立，主要是作为环境化学品的GFP转基因鱼。虽然已经进行了几个优秀的研究与斑马鱼胚胎的化学品的影响，2，3，7，8-四氯二苯并-p-二恶英（TCDD）的发育毒理学研究最广泛的日期。我们已经发现，TCDD诱导背侧中脑的细胞凋亡，伴随着局部血流量的减少，使用发展中的斑马鱼。TCDD似乎通过诱导血管内皮细胞CYP 1A产生氧化应激，导致背侧中脑局部循环衰竭和细胞凋亡。除了在毒理学上的应用外，斑马鱼胚胎的实验系统还有助于阐明遗传突变引起的先天性异常的机制。
It is widely believed that embryos and infants during development are highly sensitive to chemicals that cause serious damage to growth. However, knowledge on the mechanisms of developmental toxicity is scarce. One reason for this is limited convenient model system other than organ cultures using rodents to study the various aspects of developmental toxicology. Cultured cells are not always adequate for this purpose, since events in morphogenesis are processed through interactions with other tissues. We focused on zebrafish embryo (Danio rerio), one of the most important organisms in developmental biology. Saturation mutagenesis, applied to drosophila and nematode to define the functions of genes, has been carried out in zebrafish but almost no other vertebrate, and several thousand lines are available due to the rapid growth and transparent body of this embryo. Enhanced databases for the genome and ESTs are available at websites with abundant genetic and biological background. By targeted gene knock-down with morpholinomodified antisense oligonucleotieds (morpholinos), the translation of a specific protein can be transiently blocked for several days. Many reporter systems in vivo have been established mainly as GFP-transgenic fish for environmental chemicals. Although several excellent studies have been performed with zebrafish embryos on the effects of chemicals, the developmental toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been most extensively studied to date. We have found that TCDD induces apoptosis in dorsal midbrain with a concomitant decrease in local blood flow, using developing zebrafish. TCDD seems to produce oxidative stress through CYP1A induction in vascular endothelium, resulting in local circulation failure and apoptosis in the dorsal midbrain. In addition to applications in toxicology, an experimental system with zebrafish embryos could help to clarify the mechanism of congenital anomaly, which arises from genetic mutation.