title: Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.
abstract: Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. wswindell@genetics.med.harvard.edu
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.forename: Andrew
authors.initials: A
authors.lastname: Johnston
authors.forename: Steve
authors.initials: S
authors.lastname: Carbajal
authors.forename: Gangwen
authors.initials: G
authors.lastname: Han
authors.forename: Christian
authors.initials: C
authors.lastname: Wohn
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Xianying
authors.initials: X
authors.lastname: Xing
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Nair
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
authors.forename: Errol P
authors.initials: EP
authors.lastname: Prens
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
authors.forename: Mark R
authors.initials: MR
authors.lastname: Pittelkow
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ward
authors.forename: Johann E
authors.initials: JE
authors.lastname: Gudjonsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000627:therapeutic use; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; D000077271:Imiquimod