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

https://doi.org/10.1073/pnas.1222878110
Journal Article
Proceedings of the National Academy of Sciences, vol. 110, iss. 9, pp. 3507-3512, 2013
Authors
Junhee Seok, H. Shaw Warren, Alex G. Cuenca, Michael N. Mindrinos, Henry V. Baker, Weihong Xu, Daniel R. Richards, Grace P. McDonald-Smith, Hong Gao, Laura Hennessy, Celeste C. Finnerty, Cecilia M. López, Shari Honari, Ernest E. Moore, Joseph P. Minei, Joseph Cuschieri, Paul E. Bankey, Jeffrey L. Johnson, Jason Sperry, Avery B. Nathens, Timothy R. Billiar, Michael A. West, Marc G. Jeschke, Matthew B. Klein, Richard L. Gamelli, Nicole S. Gibran, Bernard H. Brownstein, Carol Miller-Graziano, Steve E. Calvano, Philip H. Mason, J. Perren Cobb, Laurence G. Rahme, Stephen F. Lowry, Ronald V. Maier, Lyle L. Moldawer, David N. Herndon, Ronald W. Davis, Wenzhong Xiao, Ronald G. Tompkins, Amer Abouhamze, Ulysses G. J. Balis, David G. Camp, Asit K. De, Brian G. Harbrecht, Douglas L. Hayden, Amit Kaushal, Grant E. O’Keefe, Kenneth T. Kotz, Weijun Qian, David A. Schoenfeld, Michael B. Shapiro, Geoffrey M. Silver, Richard D. Smith, John D. Storey, Robert Tibshirani, Mehmet Toner, Julie Wilhelmy, Bram Wispelwey, Wing H Wong,
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.
English