Abandon the mouse research ship? Not just yet!

Marcin F. Osuchowski, Daniel G. Remick, James A. Lederer, Charles H. Lang, Ansgar O. Aasen, Mayuki Aibiki, Luciano C. Azevedo, Soheyl Bahrami, Mihaly Boros, Robert Cooney, Salvatore Cuzzocrea, Yong Jiang, Wolfgang G. Junger, Hiroyuki Hirasawa, Richard S. Hotchkiss, Xiang An Li, Peter Radermacher, Heinz Redl, Reinaldo Salomao, Amin Subandrio W. KusumoChristoph Thiemermann, Jean Louis Vincent, Peter Ward, Yong Ming Yao, Huang Ping Yu, Basilia Zingarelli, Irshad H. Chaudry

Research output: Contribution to journalReview article

97 Citations (Scopus)

Abstract

Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

Original languageEnglish
Pages (from-to)463-475
Number of pages13
JournalShock
Volume41
Issue number6
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • burn
  • endotoxemia
  • Mouse models of critical illness
  • sepsis
  • trauma

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  • Cite this

    Osuchowski, M. F., Remick, D. G., Lederer, J. A., Lang, C. H., Aasen, A. O., Aibiki, M., Azevedo, L. C., Bahrami, S., Boros, M., Cooney, R., Cuzzocrea, S., Jiang, Y., Junger, W. G., Hirasawa, H., Hotchkiss, R. S., Li, X. A., Radermacher, P., Redl, H., Salomao, R., ... Chaudry, I. H. (2014). Abandon the mouse research ship? Not just yet! Shock, 41(6), 463-475. https://doi.org/10.1097/SHK.0000000000000153