Zebrafish: an emerging model system for human disease and drug discovery.
In vivo studies represent an essential step in drug development and currently rely largely on mice, yet limitations of mammalian models motivated the search for complementary vertebrate model systems. This review focuses on zebrafish, Danio rerio, as a facile model system to study human disease and drug responses. Zebrafish are particularly suited for this purpose because they represent a vertebrate species, their genome is sequenced, and a large number of synchronously developing, transparent embryos can be produced. Zebrafish embryos are permeable to drugs and can easily be manipulated using well-established genetic and molecular approaches. Here, we summarize recent work on drug discovery and toxicity in zebrafish embryos. In addition, we provide a synopsis of current efforts to establish disease models in zebrafish focusing on neoplasia. The results of these studies highlight the potential of zebrafish as a viable addition to established animal models by offering medium and, potentially, high throughput capabilities.
Kari
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Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Rodeck
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Dicker
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004249:DNA Damage; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D023421:Models, Animal; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000196:embryology; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
D000970:Antineoplastic Agents; D002273:Carcinogens; D009153:Mutagens