The development of new animal models is essential for the advancement of modern biomedical science. Animal models allow us to test promising drug leads, as well as understand complex pathogen-host relationships and various other critical processes in pre-clinical trial settings. We all know about the routinely used and often effective mouse model. But how much do we know about the zebrafish and its potential uses?
This beautiful patterned fish is part of the minnow family and native to the Himalayas. Zebrafish were some of the first vertebrates after frogs to be successfully cloned. They have been the subject of numerous large-scale mutagenesis and other genetic screens allowing us to better understand vertebrate developmental biology. Zebrafish have even been sent to space!
However, it is their ability to regenerate various organs as adults, including their hearts, that is so astonishing. Using various chemical transformations such as histone demethylation and the secretion of growth factors, adult zebrafish are able to turn injured tissue into juvenile stem cell-like tissue capable of repair and regeneration.
The zebrafish model and its diverse uses have huge implications for researchers looking to study regenerative therapies and novel drugs. This is particularly relevant for cardiac diseases, which cause a huge number of deaths worldwide due to their unexpected occurrence. Once injured, the human heart is only able to repair its cardiomyocytes at an approximate rate of 1% per year, and even then, the myocardium is replaced with inactive scar tissue and does not regain its proper function. Zebrafish potentially hold the key to solving this problem.
Researchers have developed numerous models to study this phenomenon in zebrafish. The most common study design involves injuring the heart and studying the way it is pieced back together to allow functional repair. The advent of various technologies, such as the genetic manipulation of various cells, has allowed scientists to reach the point where translation into humans is no longer just a far-fetched ideal.
This incredible creature has numerous other uses, too. In a drug discovery setting, the zebrafish is used as a model organism for genetic disorders, which can be modulated using compounds. Indeed, high rates of random mutagenesis can be achieved easily via exposure to the chemical mutagen ENU. Mutations can then be isolated and bred for homozygosity. This is particularly useful in cancer research where old compounds are repurposed. The zebrafish allows researchers to closely monitor tumor growth, and simultaneously relate it to a genetic change in the organism. There is also scope for infectious disease testing, as the immune system of the zebrafish is very similar to that of humans, and much more so than that of mice. In addition, the early stages of the zebrafish are transparent, thus allowing for in vivo imaging, which is another major advantage over the mouse model.
Of course, this model is not without flaws—the most glaring being that the zebrafish is not a mammal. Furthermore, interspecies and inter-individual differences in zebrafish cause difficulties in research use. However, with genetic modifications, this can be overcome.
So, is the zebrafish a useful model? The answer is a resounding yes, and an example includes the promising research recently released in the field of regenerative drug discovery. A compound known as MSI-1436 has potential uses in several diseases, and can encourage the regeneration of heart and skeletal muscles.
The zebrafish allows researchers to study complex biology in a living organism at a very modest price. Harnessing the potential of this organism will certainly benefit millions of scientists worldwide. The impact this modest creature can have on the world of scientific discovery is boundless, especially when coupled with the ever-evolving technologies in our labs.
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Marine is a Master's student at the University of Cape Town, South Africa, and specialises in mass spectrometry-based proteomics and HIV-tuberculosis co-infections. She is an avid horse-rider and loves to cook, craft, and read.