Using Zebrafish to Study Human Genetic Disease


Zebrafish is becoming a more and more popular model organism to study human genetic disease. Recent advances in genome editing, including but not limited to the CRISPR/cas technology, have made zebrafish model one of the fastest, cheapest and easiest model to generate mutations similar to the ones identified in human genetic disorders. Based on its size, zebrafish mutant embryos are also a perfect model to be used in chemical preclinical screens to identify novel molecules that are able to compensate for the partial or total inactivation of a gene. Progress in human genome sequencing has recently identified several novel alleles linked to genetic disorders that can now be tested for the identification of novel therapeutics in a zebrafish mutant modelled to phenocopy the human mutation.

Key Concepts

  • Zebrafish is a remarkable model to study human genetic diseases
  • The zebrafish genetic tool box has a novel reliable tool: the CRISPR/cas9 technology for reverse genetics
  • Zebrafish as a model for drug discovery
  • Development of zebrafish as a now tool for cure in personalised/precision medicine

Keywords: zebrafish; genetics; genomics; CRISPR; genetic disease model; drug discovery; personalised/precision medicine

Figure 1. (a) Zebrafish fills an important gap in the hierarchy of experimental model systems. (b) General overview of approaches to identify drugs or genes that modify human disease pathology. Typically mutant‐mimicking pathology or transgenic fish, for example, fish overexpressing oncogene and fluorescent reporter (green), is used in combination with compound screen or genetic screen to identify molecules or genes that modify course of disease or pathology to identify therapeutic drug candidate or gene interaction.
Figure 2. Zebrafish embryos are used for drug screening in 96 well plate (or 384 well plate). Each well contain a 1–3 zebrafish embryo and drug or a combination of drugs.
Figure 3. Schematic representation of disease‐in‐a‐fish for the use of zebrafish in drug discovery in personalised medicine. To date, this full circle is yet to be completed in an actual human patient.


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Further Reading

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Khan KM, Collier AD, Meshalkina DA, et al. (2017) Zebrafish models in neuropsychopharmacology and CNS drug discovery. British Journal of Pharmacology. DOI: 10.1111/bph.13754.

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Li M, Zhao L, Page‐McCaw PS and Chen W (2016) Zebrafish genome engineering using the CRISPR‐Cas9 system. Trends in Genetics 32 (12): 815–827.

Yoganantharjah P and Gibert Y (2017) The use of the zebrafish model to aid in drug discovery and target validation. Current Topics in Medicinal Chemistry. DOI: 10.2174/1568026617666170130112109.

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Kaslin, Jan, and Gibert, Yann(Oct 2017) Using Zebrafish to Study Human Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0027226]