Use of zebrafish to increase our understanding of diseases
One major use of zebrafish is to increase our understanding of diseases and provide disease models for therapeutic discovery.
We focus on rare inherited diseases, which together affect about one in every 10 people, even though each disease has an incidence of less than 1 in 2000 people. They frequently cause premature death in childhood and the vast majority have no approved treatments. One example is a group of diseases called Batten disease, a set of fatal childhood neurodegenerative disease that causes epilepsy, blindness, dementia and loss of function leading to a protracted period of severe disability. Batten disease is also found in many breeds of dogs and in some breeds of cattle and sheep, resulting in euthanasia before significant welfare concerns arise.
We also study epilepsy, which results in a significantly reduced quality of life for the thousands of human and veterinary patients for whom seizures are not controlled by the currently available drugs.
There is a huge need to find treatments for these diseases in both humans and veterinary species. To find treatments, we model the disease in fish and investigate those fish to find out which aspects of the disease we should be targeting with treatment. As many of the diseases we study affect children or young animals, and because we need to understand the function of proteins in the whole animal, it is useful to use externally developing embryos for our studies, for which the zebrafish model is ideally suited. The zebrafish can also be easily genetically manipulated, making it useful for modelling inherited diseases. Additionally, it produces large numbers of offspring so the experiments we do are on a large scale. This means we can screen many chemicals quickly to see if they have a positive effect on the zebrafish disease model. Such chemicals have the potential to become treatments after further study.
We are able to use the zebrafish model as a substantive body of work shows that developmental, homeostatic and metabolic processes are highly conserved between vertebrates. Thus, data derived from our models can be extrapolated to humans and other animals.
Zebrafish embryos develop externally from the mother and do not become free-feeding and regulated by ASPA legislation until 5 days old. Before this age, the zebrafish is not thought to experience pain or suffering. The diseases we model predominantly affect embryos at stages before 5 days old to minimise pain and suffering involved. To generate the embryos we experiment on we breed from genetically-altered adult zebrafish. These adults do not have the disease themselves but are regulated by ASPA because they are genetically-modified. Hence these fish contribute to the numbers included in our °ÄÃÅÍõÖÐÍõ Office returns.