Zebrafish are small fish (only growing up to 6cm in length but are usually around 4cm) with the appearance of black/blue and white stripes. Zebrafish have been interesting to research since the 1960’s and the University of Sheffield have kept Zebrafish on campus for research since 1997. But why are these little fish so important for human genetic and disease research?
These tropical fish are native to South East Asia and their larvae are transparent (making their development and inner workings easy to observe), gaining trademark stripes as they mature. Zebrafish are small and robust, easy to maintain, and cheaper than mice. These little fish produce hundreds of offspring weekly, so there is always an ample supply for testing, and they grow extremely fast, taking only a day to develop as much as a human baby does in a month! The complete genome of the zebrafish was successfully sequenced and published in 2013, containing 26,247 protein-coding genes (1,505,581,940 base pairs, just for this little fish!). In fact, zebrafish share 70% of their genes with us…so let’s see what these little fish can tell us.
84% of genes known to be associated with human diseases have a zebrafish counterpart gene. This means zebrafish can tell us a lot about diseases that afflict us, providing the opportunity to better understand these genes and how to target them effectively. The transparency of their larvae is perhaps the most crucial of the zebrafish qualities. This enables scientists to visualise cellular processes, including blood-flow and wound healing, through a microscope. Having sequenced the zebrafish genome, it is now possible to thoroughly research each disease-causing gene, understand why it causes the disease and how we can avoid this or treat it.Researchers at the University of Sheffield use genetic engineering to create alterations to the disease-causing genes and investigate the resulting effects. Their aim is to improve our understanding of the gene’s role within the disease it is associated with. They are currently using genetically modified zebrafish to better understand and hopefully find treatments for the following conditions: Parkinson’s, motor neurone disease, wound healing, cancer, cardiovascular disease, hearing and balance, optic response, hypoxia, aging, epilepsy and muscular dystrophy. They’ve already discovered a couple of potential drug targets for a few of these conditions.
As well as sharing a large number of our genes, in school, the first fact I heard about zebrafish was that they could regenerate. It is well documented that zebrafish can uniquely repair their heart muscle. If part of their heart is removed it grows back in just a few weeks. Scientists want to find out how and what specific factors are involved in this process, hoping it will help us develop ways to repair human hearts with heart failure, or those who have suffered heart attacks. Alongside their ability to regrow heart tissue, zebrafish have shown they can regain the ability to swim after a spinal cord injury. The fish are able to repair nerve damage. Researchers at the University of Edinburgh discovered that the immune system plays a large role in this mechanism. The group found that macrophages produce important molecules which dampen inflammation at the site of a spinal injury, enabling nerve cells to bridge the gap and repair lost nerve connections. Macrophages are part of our immune system, responsible for the detection and destruction of foreign material in the body (e.g. bacteria, viruses, or microorganisms causing disease). The next step for the research is to establish how these molecules work in the human body and hopefully, understand how this could be translated into a treatment for spinal injury or nerve damage patients.Having been used in research for over 50 years now, zebrafish are truly becoming one of the most important models for human disease. From nerve damage to Parkinson’s, it appears the zebrafish is able to help us understand and hopefully treat a plethora of diseases. In the future, we may have these little fish to thank for quite a lot. Here’s to the zebrafish.