Mouse Models of Psoriasis: A Comprehensive Review

Abstract

The use of preclinical animal models of psoriasis has significantly increased over the last three decades, with each model having unique strengths and limitations. Some models translate better to human disease, and many have provided unique insight into psoriasis disease pathogenesis. In this comprehensive review, we present a comparative description and discussion of genetic mouse models, xenograft approaches, and elicited methods using cytokine injections into and topical imiquimod onto mice. We provide an inclusive list of genetically modified animals that have had imiquimod applied to or cytokines injected into their skin and describe the outcomes of these manipulations. This review will provide a valuable resource for those interested in working with psoriasis animal models.

Figure 1.. Timeline of milestone discoveries in psoriasis pathogenesis and mouse models of psoriasis.

Chronological landmark discoveries made for human psoriasis pathogenesis are depicted in addition to the advent of individual mouse models of psoriasis. Each model has been placed into a broadly defined category and listed by date of publication and is called by the name used in the original paper. Mouse models that develop a psoriatic arthritis-like phenotype are listed in blue font. The timeline of therapeutic discoveries and FDA-approved drugs (brown background), including biologics (white font, dark brown background) are also presented. Discontinued drugs appear in a white background. See Table S1 for PMID and original publication citations for each animal model.

Figure 2.. Summary of mouse models of psoriasis according to category and overlap with human psoriasis.

Graphical presentation of all mouse models of psoriasis listed in Table S1 according to total number of publications for each general category (a). Total publications for specific models within each category (b). Bubble size in a and b represent number of models. Total publications for each model classified by target, excluding the imiquimod model (c). Bubble size in c represents number of unique models for each target. (GF, growth factor). (d) Bioinformatic comparison of genes and outcomes manipulated in transgenic, topical imiquimod and IL-23 intradermal injections mouse models with changes in gene expression in psoriasis patient lesional skin. (e) Reactome fold enrichment analyses identifies top pathways for each model.

Figure 3.. Comparison of psoriasis patient lesional skin with mouse psoriasiform skin.

H&E staining of lesional psoriasis skin and dorsal skin from Klk6⁺, KC-Tie2, and imiquimod (IMQ) models. Human skin is thicker than mouse skin. Acanthosis (epidermal thickening) is a key characteristic present in psoriasis patient and mouse model skin. Rete pegs occur only in psoriasis patient plaque (black stars), not mouse skin. Mouse skin has fur, more hair follicles, and hair follicle epidermis thickens in animal models of psoriasis (e.g., white stars). Mouse skin has a muscle layer called the panniculus carnosus (black arrow) not found in human skin. Psoriasis plaque and psoriasiform mouse skin contain dense immune cell infiltrate comprised of T cells, myeloid cells (not shown), and Munro-like neutrophilic microabscesses (grey arrows). Neutrophils are primarily contained to the microabscesses in plaque psoriasis and can be seen exiting the dermal vasculature (*). Psoriasiform mouse skin also contains neutrophilic microabscesses, however imiquimod skin has an abundance of neutrophils in the dermis. Scale bar = 100μm for each mouse image; scale bar = 50μm for each human image.