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The zebrafish (1981)


No tropical fish tank is complete without the zebrafish (Danio rerio), a freshwater minnow native to the Himalayan region. These stripy tiddlers have, however, become important models in biomedical research thanks to a Hungarian-born American scientist called George Streisinger, who became convinced in the 1970s that this little fish could provide deep insights into the physiology, genetics and immune systems of other vertebrates including humans. His hunch proved correct when in 1981, while at the University of Oregon, he developed and published the methods for the mutation and genetic analysis of the zebrafish with the aim of being able to study the vertebrate nervous system.

However, it soon became apparent that the zebrafish is also incredibly useful for a range of other model systems, such as studying the complexities of the vertebrate immune system.

There are two reasons why the zebrafish is such a good animal model. The first is simply that its larvae are transparent and so easy to study under the microscope, especially with fluorescently-marked proteins. The second is that during the first four to six weeks of life as a larva, the zebrafish only has the innate immune response of vertebrates – its adaptive or acquired immune response develops quite separately later on in its development.

The innate immune response is the part of the immune system honed over millions of years of evolution to recognise and respond to pathogens at the population level. The adaptive arm of the immune system, in contrast, learns to respond to threats it has already “seen” before during the life of the organism. The fact that these two mechanisms of immunity are separated in the zebrafish for several week post fertilisation, combined with their relatively small size, rapid life cycle and ease of breeding, has made the zebrafish an important model of the vertebrate immune system – a laboratory model that has in effect developed over the 450 million years of the species’ evolution.