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Publication : Genomic responses in mouse models poorly mimic human inflammatory diseases.

First Author	Seok J	Year	2013
Journal	Proc Natl Acad Sci U S A	Volume	110
Issue	9	Pages	3507-12
PubMed ID	23401516	Mgi Jnum	J:195323
Mgi Id	MGI:5477893	Doi	10.1073/pnas.1222878110
Citation	Seok J, et al. (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 110(9):3507-12

abstractText

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.

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40 Authors

Herndon DN,
Gamelli RL,
Calvano SE,
Nathens AB,
Klein MB,
Cuschieri J,
Xu W,
Xiao W,
Gibran NS,
Johnson JL,
Mindrinos MN,
Billiar TR,
Mason PH,
Hennessy L,
Moore EE,
Maier RV,
Seok J,
Finnerty CC,
Cuenca AG,
West MA,
Tompkins RG,
Sperry J,
López CM,
Brownstein BH,
Bankey PE,
Rahme LG,
McDonald-Smith GP,
Richards DR,
Gao H,
Inflammation and Host Response to Injury, Large Scale Collaborative Research Program.,
Minei JP,
Moldawer LL,
Davis RW,
Lowry SF,
Jeschke MG,
Honari S,
Baker HV,
Miller-Graziano C,
Warren HS,
Cobb JP

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