Autoantigen-Humanized Mouse Models of Bullous Pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by tense blisters and itchy erythema, predominantly affecting elderly individuals. The pathogenic autoantibodies mainly target collagen XVII (COL17), leading to subepidermal blister formation and infiltrations of immune cells, including eosinophils and neutrophils. Although systemic oral corticosteroids remain the mainstay of treatment, their use in elderly patients is often limited by serious complications and adverse effects, highlighting the unmet need for novel therapeutic targets. Several mouse models for BP have been reported; however, the inconsistency of disease induction has hindered therapeutic investigations. The active BP mouse model has emerged as a reliable system that recapitulates key disease features, making it valuable for both preclinical therapeutic studies and elucidation of BP pathophysiology. Furthermore, autoantigen-humanized mouse models, including the active BP model and the neonatal passive IgG transfer model, provide significant advantages for the development of antigen-specific therapies. Here, we describe detailed materials and methods for mouse models for BP using the COL17-humanized mouse, including the active BP mouse model and the neonatal passive IgG transfer model. Protocol modifications may be necessary when using different donor mice and antibodies. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Active BP mouse model Basic Protocol 2: Passive IgG transfer mouse model using neonatal mice.