Genomic responses in mouse models poorly mimic human inflammatory diseases

被引：2293

作者：

Seok, Junhee ^{[1
]}

Warren, H. Shaw ^{[2
]}

Cuenca, Alex G. ^{[5
]}

Mindrinos, Michael N. ^{[1
]}

Baker, Henry V. ^{[5
]}

Xu, Weihong ^{[1
]}

Richards, Daniel R. ^{[6
]}

McDonald-Smith, Grace P. ^{[7
]}

Gao, Hong ^{[1
]}

Hennessy, Laura ^{[8
]}

Finnerty, Celeste C. ^{[9
,10
]}

Lopez, Cecilia M. ^{[5
]}

Honari, Shari ^{[8
]}

Moore, Ernest E. ^{[11
]}

Minei, Joseph P. ^{[12
]}

Cuschieri, Joseph ^{[13
]}

Bankey, Paul E. ^{[14
]}

Johnson, Jeffrey L. ^{[11
]}

Sperry, Jason ^{[15
]}

Nathens, Avery B. ^{[16
]}

Billiar, Timothy R. ^{[15
]}

West, Michael A. ^{[17
]}

Jeschke, Marc G. ^{[18
]}

Klein, Matthew B. ^{[13
]}

Gamelli, Richard L. ^{[19
]}

Gibran, Nicole S. ^{[13
]}

Brownstein, Bernard H. ^{[20
]}

Miller-Graziano, Carol ^{[14
]}

Calvano, Steve E. ^{[21
]}

Mason, Philip H. ^{[7
]}

Cobb, J. Perren ^{[3
]}

Rahme, Laurence G. ^{[4
]}

Lowry, Stephen F.

Maier, Ronald V. ^{[13
]}

Moldawer, Lyle L. ^{[5
]}

Herndon, David N. ^{[9
,10
]}

Davis, Ronald W. ^{[1
]}

Xiao, Wenzhong ^{[1
,4
]}

Tompkins, Ronald G. ^{[4
]}

机构：

[1] Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat & Med, Boston, MA 02114 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care Med, Boston, MA 02114 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA

[5] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA

[6] Ingenuity Inc, Redwood City, CA 94063 USA

[7] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA

[8] Harborview Med Ctr, Dept Surg, Seattle, WA 98195 USA

[9] Univ Texas Med Branch, Shriners Hosp Children, Galveston, TX 77550 USA

[10] Univ Texas Med Branch, Dept Surg, Galveston, TX 77550 USA

[11] Univ Colorado, Dept Surg, Denver, CO 80045 USA

[12] Univ Texas SW Med Ctr Dallas, Dept Surg, Parkland Mem Hosp, Dallas, TX 75390 USA

[13] Univ Washington, Sch Med, Dept Surg, Harborview Med Ctr, Seattle, WA 98195 USA

[14] Univ Rochester, Sch Med, Dept Surg, Rochester, NY 14642 USA

[15] Univ Pittsburgh, Dept Surg, Med Ctr, Presbyterian Univ Hosp, Pittsburgh, PA 15213 USA

[16] Univ Toronto, St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada

[17] Univ Calif San Francisco, Dept Surg, San Francisco Gen Hosp, San Francisco, CA 94143 USA

[18] Univ Toronto, Div Plast & Reconstruct Surg, Dept Surg, Toronto, ON M4N 3M5, Canada

[19] Loyola Univ, Stritch Sch Med, Dept Surg, Chicago, IL 60153 USA

[20] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA

[21] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 09期

关键词：

human disease; translational medicine; inflammation; immune response; injury; LEUKOCYTE GENE-EXPRESSION; SEPSIS; MICE; RESISTANCE; TOLERANCE; DRUG;

D O I：

10.1073/pnas.1222878110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：3507 / 3512

页数：6

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