Genomic responses in mouse models poorly mimic human inflammatory diseases Journal Article

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Authors: Seok, J.; Warren, H. S.; Cuenca, A. G.; Mindrinos, M. N.; Baker, H. V.; Xu, W; Richards, D. R.; McDonald-Smith, G. P.; Gao, H; Hennessy, L.; Finnerty, C. C.; Lopez, C. M.; Honari, S.; Moore, E. E.; Minei, J. P.; Cuschieri, J.; Bankey, P. E.; Johnson, J. L.; Sperry, J.; Nathens, A. B.; Billiar, T. R.; West, M. A.; Jeschke, M. G.; Klein, M. B.; Gamelli, R. L.; Gibran, N. S.; Brownstein, B. H.; Miller-Graziano, C.; Calvano, S. E.; Mason, P. H.; Cobb, J. P.; Rahme, L. G.; Lowry, S. F.; Maier, R. V.; Moldawer, L. L.; Herndon, D. N.; Davis, R. W.; Xiao, W.; Tompkins, R. G.; Inflammation and Host Response to Injury, Large Scale Collaborative Research Program
Article Title: Genomic responses in mouse models poorly mimic human inflammatory diseases
Abstract: A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 110
Issue: 9
ISSN: 1091-6490; 0027-8424
Publisher: Unknown  
Journal Place: United States
Date Published: 2013
Start Page: 3507
End Page: 3512
Language: eng
DOI/URL:

10.1073/pnas.1222878110

10.1073/pnas.1222878110
Notes: LR: 20130507; GR: 5P50GM060338/GM/NIGMS NIH HHS/United States; GR: 5R01GM056687/GM/NIGMS NIH HHS/United States; GR: 5U54GM062119/GM/NIGMS NIH HHS/United States; GR: P01HG000205/HG/NHGRI NIH HHS/United States; GR: R24GM102656/GM/NIGMS NIH HHS/United States; JID: 7505876; CIN: Nat Methods. 2013 Apr;10(4):288; OID: NLM: PMC3587220; 2013/02/11 [aheadofprint]; ppublish