Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis
Top Cited Papers
Open Access
- 4 April 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (4), e18266
- https://doi.org/10.1371/journal.pone.0018266
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.Keywords
This publication has 59 references indexed in Scilit:
- Depletion of antigen-presenting cells by clodronate liposomes reverses the psoriatic skin phenotype in KC-Tie2 miceBritish Journal of Dermatology, 2010
- Association analyses identify six new psoriasis susceptibility loci in the Chinese populationNature Genetics, 2010
- Genome-wide association analysis identifies three psoriasis susceptibility lociNature Genetics, 2010
- Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasisNature Genetics, 2010
- Global Gene Expression Analysis Reveals Evidence for Decreased Lipid Biosynthesis and Increased Innate Immunity in Uninvolved Psoriatic SkinJournal of Investigative Dermatology, 2009
- PsoriasisThe New England Journal of Medicine, 2009
- Apoptosis and fibrosis are early features of heart failure in an animal model of metabolic cardiomyopathyInternational Journal of Experimental Pathology, 2009
- Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathwaysNature Genetics, 2009
- Database resources of the National Center for Biotechnology InformationNucleic Acids Research, 2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005