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. 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

doi:10.1073/pnas.1222878110

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 journal › Article › peer-review

2223 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 language	English (US)
Pages (from-to)	3507-3512
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	9
DOIs	https://doi.org/10.1073/pnas.1222878110
State	Published - Feb 26 2013

Keywords

Human disease
Immune response
Inflammation
Injury
Translational medicine

ASJC Scopus subject areas

General

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10.1073/pnas.1222878110

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Junhee Seok, S., H. Shaw Warren, S. W., Alex, G. C., Michael, N. M., Henry, V. B., Xu, W., Richards, D. R., McDonald-Smith, G. P., Gao, H., Hennessy, L., Finnerty, C. C., López, C. M., Honari, S., Moore, E. E., Minei, J. P., Cuschieri, J., Bankey, P. E., Johnson, J. L., Sperry, J., ... 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

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, CC, 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, DN, 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

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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.",

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AU - Junhee Seok, Seok

AU - H. Shaw Warren, Shaw Warren

AU - Alex, G. Cuenca

AU - Michael, N. Mindrinos

AU - Henry, V. Baker

AU - Xu, Weihong

AU - Richards, Daniel R.

AU - McDonald-Smith, Grace P.

AU - Gao, Hong

AU - Hennessy, Laura

AU - Finnerty, Celeste C.

AU - López, Cecilia M.

AU - Honari, Shari

AU - Moore, Ernest E.

AU - Minei, Joseph P.

AU - Cuschieri, Joseph

AU - Bankey, Paul E.

AU - Johnson, Jeffrey L.

AU - Sperry, Jason

AU - Nathens, Avery B.

AU - Billiar, Timothy R.

AU - West, Michael A.

AU - Jeschke, Marc G.

AU - Klein, Matthew B.

AU - Gamelli, Richard L.

AU - Gibran, Nicole S.

AU - Brownstein, Bernard H.

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 N.

AU - Davis, Ronald W.

AU - Xiao, Wenzhong

AU - Tompkins, Ronald G.

PY - 2013/2/26

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N2 - 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.

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KW - Immune response

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KW - Injury

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JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

Genomic responses in mouse models poorly mimic human inflammatory diseases

Abstract

Keywords

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