Humanized Mouse Models as a Tool to Study Proinflammatory Cytokine Overexpression

Molecular Biology volume 53, pages 665–680 (2019)Cite this article

Abstract

Dysregulated proinflammatory cytokine expression may result in the development of severe pathologies, such as rheumatoid arthritis, psoriasis, and neurodegenerative diseases. Transgenic mice and, in particular, those with controllable systemic overexpression of proinflammatory cytokines have recently become an essential instrument to study the molecular mechanisms underlying disease development. Importantly, many of the models are humanized by introducing a human cytokine gene, while leaving or removing the respective endogenous mouse gene. Humanized mice are especially valuable for biomedical research as they provide a relevant model to develop therapies based on blocking the pathogenic activity of a cytokine or to establish the functional significance of genome polymorphisms. The review discusses the available humanized mouse models with overexpression of key proinflammatory cytokines (TNF, IL-1β, and IL-6) and inflammatory cytokines with more specific functions (IL-8, IL-17, and IL-32) and their significance for basic and clinical research.

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Notes

  1. 1.

    When describing mouse models with transgenic overexpression of human cytokines, we hereafter use the additional letter h to denote the respective human protein (e.g., hTNF), while the protein name without the additional h refers to the mouse protein.

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ACKNOWLEDGMENTS

We are grateful to A.V. Deikin for constructing the hIL-6 Tg mouse strain at the Collective Access Center of the Institute of Gene Biology (Russian Academy of Sciences) and P.V. Matveev for help in figure preparation.

Funding

This work was supported by the Russian Science Foundation (project no. 19-75-30032).

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Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    E. A. Gorshkova, R. V. Zvartsev, M. S. Drutskaya & E. O. Gubernatorova

  2. Immunology Department, Biological Faculty, Moscow State University, 119234, Moscow, Russia

    E. A. Gorshkova & E. O. Gubernatorova

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  1. E. A. Gorshkova
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  2. R. V. Zvartsev
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  3. M. S. Drutskaya
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  4. E. O. Gubernatorova
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Correspondence to E. A. Gorshkova or E. O. Gubernatorova.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Translated by T. Tkacheva

 Abbreviations: ApoE, apolipoprotein E; ARE, AU-rich element; Cas9, CRISPR-associated protein 9; CFU, colony-forming unit; CRISPR, clustered regularly interspaced short palindromic repeat; GM-CSF, granulocyte–macrophage colony-stimulating factor; EGFP, enhanced green fluorescent protein; IL, interleukin; IL-6R, IL-6 receptor; iNOS, induced NO synthase; M-CSF, macrophage colony-stimulating factor; Th2, T helper cell type 2; TNF, tumor necrosis factor; TNFR, TNF receptor; UTR, untranslated region; ESC, embryonic stem cell.

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Gorshkova, E.A., Zvartsev, R.V., Drutskaya, M.S. et al. Humanized Mouse Models as a Tool to Study Proinflammatory Cytokine Overexpression. Mol Biol 53, 665–680 (2019). https://doi.org/10.1134/S0026893319050078

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Keywords:

  • transgenesis
  • humanization
  • mouse models
  • TNF
  • IL-6