title: Genomic responses in mouse models poorly mimic human inflammatory diseases.
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 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.
authors: Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94305, USA.
authors: Junhee
authors: J
authors: Seok
authors: H Shaw
authors: HS
authors: Warren
authors: Alex G
authors: AG
authors: Cuenca
authors: Michael N
authors: MN
authors: Mindrinos
authors: Henry V
authors: HV
authors: Baker
authors: Weihong
authors: W
authors: Xu
authors: Daniel R
authors: DR
authors: Richards
authors: Grace P
authors: GP
authors: McDonald-Smith
authors: Hong
authors: H
authors: Gao
authors: Laura
authors: L
authors: Hennessy
authors: Celeste C
authors: CC
authors: Finnerty
authors: Cecilia M
authors: CM
authors: López
authors: Shari
authors: S
authors: Honari
authors: Ernest E
authors: EE
authors: Moore
authors: Joseph P
authors: JP
authors: Minei
authors: Joseph
authors: J
authors: Cuschieri
authors: Paul E
authors: PE
authors: Bankey
authors: Jeffrey L
authors: JL
authors: Johnson
authors: Jason
authors: J
authors: Sperry
authors: Avery B
authors: AB
authors: Nathens
authors: Timothy R
authors: TR
authors: Billiar
authors: Michael A
authors: MA
authors: West
authors: Marc G
authors: MG
authors: Jeschke
authors: Matthew B
authors: MB
authors: Klein
authors: Richard L
authors: RL
authors: Gamelli
authors: Nicole S
authors: NS
authors: Gibran
authors: Bernard H
authors: BH
authors: Brownstein
authors: Carol
authors: C
authors: Miller-Graziano
authors: Steve E
authors: SE
authors: Calvano
authors: Philip H
authors: PH
authors: Mason
authors: J Perren
authors: JP
authors: Cobb
authors: Laurence G
authors: LG
authors: Rahme
authors: Stephen F
authors: SF
authors: Lowry
authors: Ronald V
authors: RV
authors: Maier
authors: Lyle L
authors: LL
authors: Moldawer
authors: David N
authors: DN
authors: Herndon
authors: Ronald W
authors: RW
authors: Davis
authors: Wenzhong
authors: W
authors: Xiao
authors: Ronald G
authors: RG
authors: Tompkins
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D002056:Burns / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000235:genetics / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014947:Wounds and Injuries / Q000235:genetics / Q000473:pathology; D055815:Young Adult
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