Zebrafish: Lab Rats of The Future, Today

zebrafish brachydanio rerio

“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. Indispensable in medical research, they might even replace lab rats as the model animal of choice in the future.

An Introduction to Zebrafish

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.

zebra fish
Not exactly the fish you’re looking for. (Flickr)

The use of zebrafish (Danio rerio) as a laboratory model started in the 1960s, so they’ve actually been in labs for awhile. These tiny fish are found in the wild throughout southeast Asia and kept as pets in aquariums. However, their genome was only 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.

zebrafish embryo microscope
Zebrafish embryo under a light microscope!

Models of Disease

Heart Disease

It just so happens that similar pathways and genes that govern our 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. This remarkable ability is something that is being studied for its potential application in human tissue.

Zebrafish are also utilized in early medicinal chemistry programs. Huge libraries of many thousands of compounds that might be the next best drug for heart disease have 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 observe how 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.

Various Forms of Cancer

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 easy; it can be as simple as dissolving carcinogens in their 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. This allows for incredible visualization of its organs or tumors in real-time in a living fish.

tumor on zebrafish head
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.

human vs zebrafish cholangiocarcinoma cancer cells
The 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 barely scratches the surface of what zebrafish research has uncovered so far. The possibilities for further studies are endless. In the future, perhaps zebrafish will even be used to great effect in preclinical trials due to their similarity to humans.

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 fascinating 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.

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