Zebrafish as an animal model for biomedical research

Abstract

Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic compound screenings, and other biomedical research applications. With the impactful developments of CRISPR and next-generation sequencing technology, disease modeling in zebrafish is accelerating the understanding of the molecular mechanisms of human genetic diseases. These efforts are fundamental for the future of precision medicine because they provide new diagnostic and therapeutic solutions. This review focuses on zebrafish disease models for biomedical research, mainly in developmental disorders, mental disorders, and metabolic diseases.

Fig. 1. Development of the central nervous system in zebrafish.

a Detection of early neuronal precursor cells by whole-mount in situ hybridization with a pan-neuronal marker, huC, at the neural plate stage (10.5 h after fertilization). Unpublished data. b Immunostaining of axonal growth in the spinal cord of one-day-old zebrafish. Double-staining with anti-gicerin antibody and anti-HNK-1 antibody. c Confocal image of myelin structure in an isolated adult zebrafish brain visualized by mbp promoter-driven membrane-tagged GFP, Tg(mbp:mEGFP). Arrows indicate the olfactory, optic, and otic nerves. Unpublished data.

Fig. 2. Subcellular organelles in the developing zebrafish embryos.

a Using transgenic zebrafish lines 5 dpf, mitochondria, Tg(Xla.Eef1a:MLS-EGFP), and peroxisomes, Tg(Xla. Eef1a:RFP-SKL), in the skin of the developing larva are visualized. b Motile cilia (green) in the hindbrain 4th ventricle are visualized with anti-acetylated tubulin antibody, and nuclei are shown in red. Unpublished data.

Fig. 3. Bile duct formation in the developing zebrafish liver 6 dpf.

a, b Using a transgenic zebrafish line, Tg(Tp1:H2BmCherry), biliary epithelial cell nuclei are labeled red. The bile duct in the developing liver is visualized using the BODIPY FL-C5 dye (a) or the anti-cytokeratin 18 antibody (b). Unpublished data.