Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

PLOS ONE, Apr 2011

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.

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Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

et al. (2011) Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis. PLoS ONE 6(4): e18266. doi:10.1371/journal.pone.0018266 Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis William R. Swindell 0 Andrew Johnston 0 Steve Carbajal 0 Gangwen Han 0 Christian Wohn 0 Jun Lu 0 Xianying Xing 0 Rajan P. Nair 0 John J. Voorhees 0 James T. Elder 0 Xiao-Jing Wang 0 Shigetoshi Sano 0 Errol P. Prens 0 John DiGiovanni 0 Mark R. Pittelkow 0 Nicole L. Ward 0 Johann E. Gudjonsson 0 Stefan Bereswill, Charite-University Medicine Berlin, Germany 0 1 Department of Genetics, Harvard Medical School , Boston , Massachusetts, United States of America, 2 Department of Dermatology, University of Michigan Medical School , Ann Arbor , Michigan, United States of America, 3 Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin , Austin, Texas , United States of America, 4 Departments of Pathology, Otolaryngology and Dermatology, University of Colorado, Denver, Colorado, United States of America, 5 Departments of Immunology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands , 6 Department of Dermatology, Mayo Clinic , Rochester , Minnesota, United States of America, 7 Ann Arbor Veterans Affairs Hospital , Ann Arbor , Michigan, United States of America, 8 Department of Dermatology, Kochi Medical School, Kochi University , Okocho, Nankoku , Japan , 9 Departments of Dermatology and Rheumatology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands , 10 Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin , Austin, Texas , United States of America, 11 Division of Pharmacology & Toxicology, Dell Pediatric Research Institute, The University of Texas at Austin , Austin, Texas , United States of America, 12 Department of Dermatology and the Murdough Family Center for Psoriasis, Case Western Reserve University and University Hospitals, Case Medical Center , Cleveland, Ohio , United States of America 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 (K5Tie2, 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. - Funding: This work was supported by the Babcock Endowment to Dr. Gudjonsson and Dr. Johnston, the Taubman Medical Research Institute support (Frances and Kenneth Eisenberg Emerging Scholar) and the Dermatology Foundation to Dr. Gudjonsson. The project described was supported by NIH grant number CA76520 to Dr. DiGiovanni, AR052889 and AR054966 to Dr. Elder, GM70966, CA79998 and CA89849 to Dr. Wang and P30AR39750 and P50AR05508, National Psoriasis Foundation and the Murdough Family Center for Psoriasis to Dr. Ward. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Psoriasis is a chronic inflammatory disease that leads to widespread development of erythematous plaques with adherent silvery scales. The disease is believed to be primarily mediated by T-cells, which release cytokines that stimulate keratinocyte (KC) hyperproliferation and altered differentiation [1,2]. Development of a single suitable animal model would greatly facilitate research on the mechanism(s) of action that drive inflammatory and autoimmune proce (...truncated)


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William R. Swindell, Andrew Johnston, Steve Carbajal, Gangwen Han, Christian Wohn, Jun Lu, Xianying Xing, Rajan P. Nair, John J. Voorhees, James T. Elder, Xiao-Jing Wang, Shigetoshi Sano, Errol P. Prens, John DiGiovanni, Mark R. Pittelkow, Nicole L. Ward, Johann E. Gudjonsson. Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis, PLOS ONE, 2011, Volume 6, Issue 4, DOI: 10.1371/journal.pone.0018266