Zebrafish as models of human disease and drug development

Photo of zebrafish housed at a research institute. By Karol Głąb CC BY-SA 3.0. via Wikimedia Commons

Who would have thought tiny fish could lead to big advances in medicine? Zebrafish (Danio rerio) and mammals have similar anatomy and physiology of the brain, eyes, gut, and cardiovascular systems. Some of the reasons why these fish are good models to understand cardiovascular physiology were recently explored in a new article published in Physiological Reviews.

Animal models are used in research that seeks to understand both normal physiological mechanisms as well as mechanisms related to disease. Because of their small size, zebrafish are easy to house in a laboratory. Studies of early development can also be easily performed using zebrafish embryos as they are transparent and develop externally. Their relatively short lifespans along with recent advances in the ability to alter genes allow for rapid examination of the effects of genetic mutations on development.

The focus of the review article written by Gut et al., was on the usefulness of zebrafish as models for cardiovascular and metabolism-related diseases. I was impressed to find out that zebrafish and humans share similar electrical patterns (EKG) of the heart as well as heart rates of 60-100 beats per minute (as compared to mice with heart rates around 600 beats/min). They also experience some of the same pathologies related to electrical conduction in the heart. In addition, the zebrafish heart expresses 96% of the genes that are associated with cardiomyopathy in humans, making them useful models in which to improve understanding as well as develop new therapies for heart disease. What is most unique about the zebrafish heart, however, is that it can regenerate. Researchers are hoping to unlock the secrets of this process in order to help regenerate hearts that have been damaged by heart attacks. Although given the relative simplicity of the zebrafish heart, this may prove challenging.

Similar to humans, researchers have found that feeding zebrafish a fat-enriched diet promotes the development of obesity, insulin resistance, fatty liver disease as well as atherosclerosis. Research has led to the discovery of how a gene that is associated with risk for developing type 2 diabetes is involved in regulating where fats are stored in the body. Another advantage to zebrafish is the discovery of a similar mechanism that causes atherosclerosis as in humans, whereas rodents do not develop the disease unless genetically manipulated. Similar to the heart, insulin-producing cells of the zebrafish pancreas are capable of regenerating, which researchers hope may lead to new therapies for the treatment of type 1 diabetes.

Zebrafish have also proved useful models in which to examine the re-purposing of old drugs as well as the creation of new drugs for the treatment of bone-related diseases, as well as cancer, multiple sclerosis, and epilepsy, just to name a few.

Source:

P Gut, S Reischauer, DYR Stainier, R Arnaout. Little Fish, Big Data: Zebrafish as a Model for Cardiovascular and Metabolic Disease. Physiological Reviews. Published 3 May 2017, Vol. 97, no. 3, pages 889-938. DOI: 10.1152/physrev.00038.2016