Journal Article

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

DiGiovanni, John, Elder, James T., Nair, Rajan P., Xing, Xianying, Johnston, Andrew, Swindell, William R., Prens, Errol P., Pittelkow, Mark R., Wang, Xiao-Jing, Wohn, Christian, Ward, Nicole L., Han, Gangwen, Voorhees, John J., Sano, Shigetoshi, Lu, Jun, Carbajal, Steve, Gudjonsson, Johann E.

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Adolescent / Adult / Aged / Aminoquinolines - therapeutic use / Analogies / Analysis / Animal models / Animals / Bayesian analysis / Bioinformatics / Biology / Biosynthesis / Cytokines - genetics / Cytokines - metabolism / Departments / Dermatology / Disease / Disease Models, Animal / Divergence / Epidermis - metabolism / Experiments / Gene expression / Gene Expression Profiling - methods / Genetic aspects / Genomes / Genomics / Genomics - methods / Growth factors / Health aspects / Homeostasis / Humans / Imiquimod / Keratin / Keratinization / Keratinocytes - metabolism / Kinases / Laboratories / Lesions / Leukocytes - immunology / Medical schools / Medicine / Mice / Middle Aged / Mitosis - genetics / Otolaryngology / Pediatrics / Phenotype / Psoriasis / Psoriasis - genetics / Psoriasis - immunology / Psoriasis - metabolism / Psoriasis - pathology / Receptor Protein-Tyrosine Kinases - genetics / Receptor, TIE-2 / Rodents / Skin / Skin diseases / Statistical analysis / Toxicology / Transcription / Transcription (Genetics) / Transcription, Genetic / Transforming growth factors / Transgenic animals / Young Adult