Comparative Aspects of Alternative Laboratory Fish Models

Abstract

If it were possible to ask a question to the late George Streisinger, I would be very interested in asking him why did he decide on zebrafish when he first looked around in the pet shop for an economical and convenient vertebrate model? Would he have made a different choice on the basis of the papers of Hinegardner,1,2 in which the genome sizes of over 100 fish species were described? Would he have made a different choice had he been aware of the complex neural functions provided by anabantid fishes, all sharing the advantages of zebrafish that are quoted so many times in reviews, lectures, and grant applications? This provocative question is asked to invite discussion about model systems: is it reasonable to promote alternative fish species alongside the canonical zebrafish3 as economical and convenient vertebrate models for studies that address genetic questions in different disciplines from physiology and neurosciences to toxicology and evolution. Many of the 25,000 or so fish species have high fecundity, short generation time, transparent embryos, and easy breeding protocols similar to zebrafish. This is of course not to question the justification for the role zebrafish plays in genetics. It makes perfect sense to focus on a single teleost model in order to concentrate the limited resources and expensive investments. However, as the zebrafish is now being used for research in new areas that extend well beyond developmental genetics, including aging, cancer, and behavior, to name just a few, an obvious question is, does the zebrafish always provide the best context for such research and could alternatives also be considered to complement the zebrafish (and medaka) system(s)? Still, why bother about alternatives when the zebrafish and, alongside of it, medaka, have become major players in genetic research, with at least one paper per week appearing in top biomedical journals. The nearly complete genome sequence, the availability of fine genetic and physical maps, half a million ESTs, thousands of mutants, and the tremendous amount of knowledge about zebrafish biology that has been gathered in the last 3 decades all contribute to make the zebrafish the popular model that it is today. This arsenal of molecular and genetic tools not only supports the continued use of zebrafish but also provides the basic data needed for comparative studies that will bring alternative models back into the spotlight. In the past, comparative studies on different species were restricted to descriptive assays. Now “reference” species such as zebrafish make it possible to conduct comparative studies at the molecular level to address questions such as evolutionary processes that lead to speciation or the diversity of morphologies. One can now apply the candidate