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On the value of zebrafish outbred strains in neurobehavioral research

Lab Animal volume 51, pages 5–6 (2022)Cite this article

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To the Editor — The zebrafish (Danio rerio) is an important model organism in biomedical research. However, unlike the availability of numerous well-characterized inbred strains in mice1, there are remarkably fewer inbred and outbred strains in zebrafish, which may impede their utility in biomedicine. A recent Perspective2 describes the history of the AB zebrafish strain, encouraging researchers to provide detailed information on the origin and genetic makeup of the zebrafish strains they use, consistent with other (e.g., mammalian) model organisms. In rodents, inbred strains have been traditionally preferred over outbred stocks in wide-ranging biomedical research3, stemming from the assumption that phenotypic variability observed in inbred laboratory animals is a priori lower than in outbred animals. However, recent evidence (based on a systematic review of the primary literature and comparing data for inbred and outbred mice tested for the same traits) reveals that only few measures in inbred mouse strains have coefficients of variation lower than in outbred mice4, whereas most measures do not differ, and some measures yield higher variance in inbred than in outbred mice4.

This conclusion is important both conceptually and practically, since it shows that outbred mice are phenotypically stable for experiments using sample sizes comparable to inbred strain studies4 and may, in fact, present a reduced phenotypical variance in response to environmental factors5. Furthermore, animal colonies are prone to genetic drift – a tendency of genes to constantly evolve even in the absence of selective forces, mostly due to spontaneous neutral mutations that disappear or become fixed in a population at random6. As such, genetic and phenotypic variance may occur in inbred strains as well, potentially becoming a critical contributing factor to data reproducibility crisis7, especially given that these strains are often perceived as ‘variance-prone’ because they are inbred. By contrast, outbred mouse populations, complementing inbred strains, may provide a powerful experimental platform for appropriately accounting for the background genetic variation on which human disease manifests4.

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Authors and Affiliations

  1. Bioscreening Platform, Southwest University, Chongqing, China

    Murilo S. de Abreu & Allan V. Kalueff

  2. Laboratory of Cell and Molecular Biology and Neurobiology, Moscow Institute of Physics and Technology, Moscow, Russia

    Murilo S. de Abreu & Elena V. Petersen

  3. Bioscience Institute and Graduate Program in Environmental Sciences, University of Passo Fundo, Passo Fundo, RS, Brazil

    Murilo S. de Abreu & Ana C. V. V. Giacomini

  4. Institute of Experimental Medicine, Almazov National Medcial Research Center, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia

    Konstantin A. Demin

  5. Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia

    Konstantin A. Demin

  6. Granov Russian Scientific Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia

    Konstantin A. Demin

  7. Novosibirsk State University, Novosibirsk, Russia

    Konstantin A. Demin & Allan V. Kalueff

  8. School of Pharmacy, Southwest University, Chongqing, China

    Allan V. Kalueff

  9. Ural Federal University, Ekaterinburg, Russia

    Allan V. Kalueff

  10. Neuroscience Program, Sirius University, Sochi, Russia

    Allan V. Kalueff

Authors
  1. Murilo S. de Abreu
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  2. Ana C. V. V. Giacomini
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  3. Konstantin A. Demin
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  4. Elena V. Petersen
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  5. Allan V. Kalueff
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Corresponding authors

Correspondence to Murilo S. de Abreu or Allan V. Kalueff.

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Competing interests

The authors declare no conflicts of interest. K.A.D. and A.V.K. are supported by the Russian Science Foundation (RSF) grant 20-65-46006. The study used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684).

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de Abreu, M.S., Giacomini, A.C.V.V., Demin, K.A. et al. On the value of zebrafish outbred strains in neurobehavioral research. Lab Anim 51, 5–6 (2022). https://doi.org/10.1038/s41684-021-00891-z

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