Psoriasis is a complex chronic inflammatory and autoimmune disease; therefore, reliable and human-relevant animal models are essential for preclinical drug testing and mechanistic studies. SKH-1 mice, which lack functional hair follicles and display a thickened epidermis that more closely resembles human skin than that of C57BL/6 mice, represent a potential psoriasis model, but their suitability remains uncertain. In this study, proliferation, barrier function, differentiation, and inflammatory responses were assessed in the imiquimod (IMQ)-induced dermatitis model of SKH-1 mice using qRT-PCR, immunofluorescence, and flow cytometry. Transcriptomic profiling via RNA sequencing was performed on total RNA from lesional and non-lesional skin of IMQ-induced SKH-1 mice, IMQ-induced C57BL/6 mice, and human psoriatic skin. A psoriasis-like mouse model was also established in SKH-1 mice to evaluate its utility for recurrence studies. The results showed that the IMQ-induced SKH-1 mouse model exhibited hyperproliferation, hypodifferentiation, barrier disruption, and excessive inflammatory responses similar to human psoriasis. Transcriptomic analysis further highlighted the advantages and complementarity of this model in studying psoriasis pathogenesis, and the established recurrence model provided a suitable tool for investigating the mechanisms of psoriasis recurrence. This study compared the transcriptomic signatures of lesional skin between IMQ-induced SKH-1 and C57BL/6 mice and demonstrated that the SKH-1 model can recapitulate vascular dysregulation and disease recurrence, indicating that it serves as a valuable complementary tool for probing psoriasis pathogenesis.
