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Clinical Implication of Zebrafish-Based Developmental Toxicology

                     

2019/02/19

From the viewpoint of animal welfare, the 3R principle of replacing it with a method that does not use laboratory animals as much as possible (Reduction), reducing the number of animals used (Reduction), and reducing pain to laboratory animals (Refinement) is required. An in vitro test as an animal experiment alternative method contributes to animal welfare, and it has advantages such as high sensitivity, high reproducibility, high throughput evaluation of a large number of test substances. However, the limit of the in vitro test method was recognized, and it became clear that there are many fields where in vivo animal experiments are indispensable. Zebrafish as a model animal responding to this task has high genomic homology with mammals and humans as vertebrates, easy to multipurpose and breeding management, in vitro fertilization, organ formation is surprisingly fast And many other superiorities are recognized, and it is first used internationally for developmental toxicity testing. Therefore, we report about the features of developmental toxicity test by zebrafish as an alternative method, especially the characteristics in extrapolation to human. First of all, genome homology in human disease-related genes is 82%, and genomic editing such as CRISPRs, which has developed rapidly recently, is one of the model organisms most widely applied. As a result, high-throughput analysis of the developmental toxicity mechanism becomes possible, and we provide information on the basis of developmental toxicology in the future in the future. In particular, a comprehensive study of zebrafish whole single cell transcriptome in a recently reported (Science 2018; 360: 6392) normal development process is thought to enhance extrapolation to humans in the future zebrafish developmental toxicity test I will. That is, zebrafish developmental toxicity testing has evolved into next-generation research protocols due to homology in the transcriptome as well as the similarity of phenomena in the developmental toxicity of humans and zebrafish.

関連リンク

Department of Systems Pharmacology Mie University Graduate School of Medicine

Mie University Medical Zebrafish Research Center