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.

Langerin neg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice

“…Hence, IMQ-induced psoriasiform skin disease is indeed mediated exclusively via MyD88-dependent signaling. To confirm the functional deficiency in MyD88 LSL mice at the molecular level, we analyzed the expression of selected psoriasisrelated transcripts in the skin (17). Topical IMQ treatment resulted in significantly increased expression of Keratin-16 (K16), S100A7, and IL-17A in back skin of wild-type but not MyD88 LSL mice (Fig.…”

Proteomics of Skin Proteins in Psoriasis: From Discovery and Verification in a Mouse Model to Confirmation in Humans

“…We utilized a gel-based label-free MS proteomic approach to fractionate and identify differentially expressed proteins in the skin of an established mouse model of psoriasis, the KC-Tie2 mouse (7,21). We identified 5482 peptides that mapped to 1281 proteins, of these, 105 proteins were either increased or decreased by more than twofold in KC-Tie2 skin.…”

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

“…GRHL3 was upregulated in human psoriasis lesions, where its expression correlated with psoriasis-associated cytokine activity. Furthermore, in imiquimod-treated (IMQ-treated) mice, a frequently used model of psoriasis (22)(23)(24), loss of Grhl3 facilitated formation of lesions, delayed their resolution, and conferred treatment resistance, which suggests that a GRHL3-regulated repair pathway suppresses disease activity. Thus, despite being dispensable during normal epidermal homeostasis, Grhl3 was again required for barrier repair after immune-mediated epidermal damage in adult skin.…”