Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Of mice and men: what rodent models don't tell us

Cellular & Molecular Immunology volume 10, pages 284–285 (2013)Cite this article

Work recently published in PNAS by The Inflammation and Host Response to Injury, Large Scale Collaborative Research Program1 compared the transcriptional responses in peripheral blood to inflammatory injuries (burns, blunt force trauma) and to endotoxin in human patients and in corresponding mouse models. The results were startling: while the human patients showed similar transcriptional responses to burns, trauma and endotoxemia, the mouse models showed little correlation either to each other or the human response. These differences extended beyond acute gene response and were also apparent in markedly slower recovery from injury, with gene expression not returning after weeks or months in patients as opposed to days in mouse models.

The results of this study shed light on an ongoing problem in therapeutic development. Approximately 90% of the drugs reported to have clinical efficacy in high profile journals based on animal models fail in clinical trials.2 Drugs to treat sepsis and acute inflammation have a much worse track record in clinical trials, with all ∼150 drugs trialed to date failing.1 This report highlights a startling example of how the in vivo models used in preclinical drug development can bear little relationship to the human diseases at the transcriptional level. Given the similarity between the human responses to pro-inflammatory stimulation, and the divergent responses in mice it would be easy to conclude that in the ∼75 million years3 since humans and mice shared a common ancestor there has been tremendous divergence in the way in which inflammatory responses are generated and resolved. Indeed, there is strong evidence to support this view in the data mining reported by the authors, who show that systematic regulation of entire pathways associated with inflammatory responses occurs across human inflammation. This coordinated response does not occur across mouse models. The authors then examined other published datasets further strengthening the broad and general nature of their findings.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 2013; 110: 3507–3512.

    Article  CAS  PubMed  Google Scholar 

  2. van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O'Collins V et al. Can animal models of disease reliably inform human studies? PLoS Med 2010; 7: e1000245

    Article  PubMed  PubMed Central  Google Scholar 

  3. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P et al. Initial sequencing and comparative analysis of the mouse genome. Nature 2002; 420: 520–562.

    Article  CAS  PubMed  Google Scholar 

  4. Wiersinga WJ . Current insights in sepsis: from pathogenesis to new treatment targets. Curr Opin Crit Care 2011; 17: 480–486.

    Article  PubMed  Google Scholar 

  5. Mitka M . Drug for severe sepsis is withdrawn from market, fails to reduce mortality. JAMA 2011; 306: 2439–2440.

    CAS  PubMed  Google Scholar 

  6. Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL . Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 2012; 12: 786–798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Drake AC, Chen Q, Chen J . Engineering humanized mice for improved hematopoietic reconstitution. Cell Mol Immunol 2012; 9: 215–224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA

    Adam C Drake

Authors
  1. Adam C Drake
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adam C Drake.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drake, A. Of mice and men: what rodent models don't tell us. Cell Mol Immunol 10, 284–285 (2013). https://doi.org/10.1038/cmi.2013.21

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2013.21

This article is cited by

Search

Advanced search

Quick links