Genomic responses in mouse models poorly mimic human inflammatory diseases

Seok Junhee Seok, Shaw Warren H. Shaw Warren, G. Cuenca Alex, N. Mindrinos Michael, V. Baker Henry, 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. NathensTimothy 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

Research output: Contribution to journalArticlepeer-review

1774 Scopus citations

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 showthat, 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., R2 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 onmouse models to study human inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)3507-3512
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number9
DOIs
StatePublished - Feb 26 2013

Keywords

  • Human disease
  • Immune response
  • Inflammation
  • Injury
  • Translational medicine

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Genomic responses in mouse models poorly mimic human inflammatory diseases'. Together they form a unique fingerprint.

Cite this