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 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 & 19 others 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 Herndon, Ronald W. Davis, Wenzhong Xiao, Ronald G. Tompkins

Research output: Contribution to journalArticle

1524 Citations (Scopus)

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

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Translational Medical Research
Biomedical Research
Animal Models
Clinical Trials
Pharmaceutical Preparations
Genes
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Junhee Seok, S., H. Shaw Warren, S. W., Alex, G. C., Michael, N. M., Henry, V. B., Xu, W., ... Tompkins, R. G. (2013). Genomic responses in mouse models poorly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences of the United States of America, 110(9), 3507-3512. https://doi.org/10.1073/pnas.1222878110

Genomic responses in mouse models poorly mimic human inflammatory diseases. / Junhee Seok, Seok; H. Shaw Warren, Shaw Warren; Alex, G. Cuenca; Michael, N. Mindrinos; Henry, V. Baker; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 9, 26.02.2013, p. 3507-3512.

Research output: Contribution to journalArticle

Junhee Seok, S, H. Shaw Warren, SW, Alex, GC, Michael, NM, Henry, VB, Xu, W, Richards, DR, McDonald-Smith, GP, Gao, H, Hennessy, L, Finnerty, C, López, CM, Honari, S, Moore, EE, Minei, JP, Cuschieri, J, Bankey, PE, Johnson, JL, Sperry, J, Nathens, AB, Billiar, TR, West, MA, Jeschke, MG, Klein, MB, Gamelli, RL, Gibran, NS, Brownstein, BH, Miller-Graziano, C, Calvano, SE, Mason, PH, Cobb, JP, Rahme, LG, Lowry, SF, Maier, RV, Moldawer, LL, Herndon, D, Davis, RW, Xiao, W & Tompkins, RG 2013, 'Genomic responses in mouse models poorly mimic human inflammatory diseases', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 9, pp. 3507-3512. https://doi.org/10.1073/pnas.1222878110
Junhee Seok, Seok ; H. Shaw Warren, Shaw Warren ; Alex, G. Cuenca ; Michael, N. Mindrinos ; Henry, V. Baker ; Xu, Weihong ; Richards, Daniel R. ; McDonald-Smith, Grace P. ; Gao, Hong ; Hennessy, Laura ; Finnerty, Celeste ; López, Cecilia M. ; Honari, Shari ; Moore, Ernest E. ; Minei, Joseph P. ; Cuschieri, Joseph ; Bankey, Paul E. ; Johnson, Jeffrey L. ; Sperry, Jason ; Nathens, Avery B. ; Billiar, Timothy R. ; West, Michael A. ; Jeschke, Marc G. ; Klein, Matthew B. ; Gamelli, Richard L. ; Gibran, Nicole S. ; Brownstein, Bernard H. ; Miller-Graziano, Carol ; Calvano, Steve E. ; Mason, Philip H. ; Cobb, J. Perren ; Rahme, Laurence G. ; Lowry, Stephen F. ; Maier, Ronald V. ; Moldawer, Lyle L. ; Herndon, David ; Davis, Ronald W. ; Xiao, Wenzhong ; Tompkins, Ronald G. / Genomic responses in mouse models poorly mimic human inflammatory diseases. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 9. pp. 3507-3512.
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AU - Henry, V. Baker

AU - Xu, Weihong

AU - Richards, Daniel R.

AU - McDonald-Smith, Grace P.

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AU - Finnerty, Celeste

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AU - Moore, Ernest E.

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AU - Cuschieri, Joseph

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AU - Johnson, Jeffrey L.

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AU - Nathens, Avery B.

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AU - West, Michael A.

AU - Jeschke, Marc G.

AU - Klein, Matthew B.

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AU - Gibran, Nicole S.

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AU - Miller-Graziano, Carol

AU - Calvano, Steve E.

AU - Mason, Philip H.

AU - Cobb, J. Perren

AU - Rahme, Laurence G.

AU - Lowry, Stephen F.

AU - Maier, Ronald V.

AU - Moldawer, Lyle L.

AU - Herndon, David

AU - Davis, Ronald W.

AU - Xiao, Wenzhong

AU - Tompkins, Ronald G.

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