Zebrafish: Lab Rats of The Future, Today

“Such an exotic name!” you exclaim, “Surely it must be some elusive endangered African species that can only be found in two specific wetlands in the Congo Basin?”
Well, the zebrafish is indeed exotic, but in a different context – the importance of which is far greater than one might bestow upon this little creature.

Lab mice have long been the perfect vertebrate model, accelerating clinical research in almost every field by providing a platform for predictive studies. Then this little fish swims along, carrying with them a package of remarkable assets that have made scientists fall seriously in love with them. Heck, we’ve even sent them into space.

An Introduction to Zebrafish

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No. (Flickr)

The use of zebrafish (Danio rerio) as a laboratory model started in to 1960s, so they’ve been around awhile. These tiny fish are found in the wild throughout southeast Asia and kept as pets in aquariums. Their genome was fully sequenced back in 2013, and they’ve never looked back since.

What’s the Big Deal?

Apart from being easy to breed and having incredible growth rates, these fish have a surprisingly similar genetic makeup compared to humans (84% of genes associated with human disease have a zebrafish counterpart1) which extends to them sharing all the major organs and tissues as us!

They were first a subject of scientific interest due to their transparent embryos making them ideal for developmental biology studies, allowing for their physiology to be studied using nothing more than a microscope.

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Zebrafish embryo under a light microscope!

Heart Disease

In a very loose sense, the same pathways and genes that made my heart and your heart are also responsible for switching on heart development in zebrafish embryos. Yet, in their larval stage zebrafish are able to regenerate their heart tissue – which is something that is being studied for its application in humans.

The cherry on top is that a huge library of many thousands of compounds that might be the next best drug for heart disease has been established, as with zebrafish they are very quickly screened to see if the compounds have an effect. We can ‘switch’ on and off genes  through cloning and see how the zebrafish re-grows vessels and repairs damage. The idea here is that if we could switch the right genes on in humans then we could live longer and survive better after a heart attack.

Cancer Models

The last few decades have seen a huge increase in cancer research, with more and more funding pouring in to accelerate this area of study. Inducing cancer in fish is relatively easier due to the simplicity of dissolving carcinogens in water for extended periods of time. Zebrafish are special however, in that even adult fish are small and transparent enough such that fluorescent markers can be introduced into its body, allowing for the visualization of its organs or tumors in real time in a living fish.

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A tumor transplanted onto a zebrafish. (Flickr)

Zebrafish tumors are also expressed similarly to human ones, along with being fully transplantable and able to be genetically mapped. The mapping of zebrafish oncogenes has already been the driving force behind the identification of cancer causing mutations in humans.

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The appearance of a histology of cholangiocarcinoma in human and zebrafish is remarkably similar, showing atypical nuclei, haphazard arrangement of irregularly shaped glands, and increased mitotic activity. (Source)

Zebrafish have been used to create models of a range of cancer types, including melanoma, leukemia, pancreatic cancer and hepatocellular carcinoma2.

This article scratches the surface of what zebrafish research has uncovered so far. While the mouse may still be the ideal disease model owing to the tools that have been developed over the years, it won’t be long before the development of zebrafish research catches up. What a great little creature!

Reference:

  1. Howe, K., Clark, M. D., Torroja, C. F., Torrance, J., Berthelot, C., Muffato, M., … & McLaren, S. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature, 496(7446), 498-503.
  2. Liu, S., & Leach, S. D. (2011). Zebrafish models for cancer. Annual Review of Pathology: Mechanisms of Disease, 6, 71-93.
  3. Amatruda, J. F., Shepard, J. L., Stern, H. M., & Zon, L. I. (2002). Zebrafish as a cancer model system. Cancer cell, 1(3), 229-231.