PUBLICATION
Zebrafish as a novel experimental model for developmental toxicology
- Authors
- Teraoka, H., Dong, W., and Hiraga, T.
- ID
- ZDB-PUB-030805-3
- Date
- 2003
- Source
- Congenital anomalies 43(2): 123-132 (Journal)
- Registered Authors
- Dong, Wu, Teraoka, Hiroki
- Keywords
- arylhydrocarbon receptor, cytochrome P450 1 A, developmental toxicology, dioxin, gene knock-down, morpholinos, TCDD, zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Dioxins/toxicity
- Embryo, Nonmammalian/drug effects
- Mesencephalon/blood supply
- Models, Animal*
- Toxicology*
- Zebrafish/embryology*
- PubMed
- 12893971 Full text @ Congenit. Anom. (Kyoto)
- CTD
- 12893971
Citation
Teraoka, H., Dong, W., and Hiraga, T. (2003) Zebrafish as a novel experimental model for developmental toxicology. Congenital anomalies. 43(2):123-132.
Abstract
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 morpholino-modified 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 themechanism of congenital anomaly, which arises from genetic mutation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping