A Hairless Mouse Model for Vitiligo: Enhancing Preclinical Therapeutic Evaluation.

Abstract

Vitiligo is an autoimmune disease that targets melanocytes, and preclinical models of the disease can strongly promote the development of new treatments. This study introduces a vitiligo model using hairless hk14-SCF Tg mice, whose melanocyte distribution closely mimics that of human skin, enabling comprehensive therapeutic evaluation. Two methods were used to induce vitiligo: (i) hairless hk14-SCF Tg mice received bone marrow-derived dendritic cells pulsed with the melanocyte-specific peptide gp100 and CD8T cells targeting gp100 (PMEL CD8T cells), and (ii) hk14-SCF Tg mice were crossbred with PMEL TCR transgenic mice without additional treatment. Skin samples were subsequently analyzed using immunohistochemistry, flow cytometry, bulk RNA sequencing, and cytokine assays, confirming that the mechanisms that drive vitiligo in this model closely resemble those of prior mouse models and patients with vitiligo. Various treatments, including UV irradiation, topical corticosteroids, and a Jak inhibitor, were tested, and all significantly reduced vitiligo-affected areas, as verified through objective ImageJ analysis. In conclusion, this model addresses key limitations of previous models, offering a robust platform for preclinical treatment evaluation and potentially accelerating clinical translation.