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Animal models of human diseases are very useful to better understand their pathomechanism and to develop new therapies. However, due to the differences among different species, it is sometimes difficult to reproduce reliable diseases phenotype in animals. Bullous pemphigoid is the most common autoimmune blistering skin disease, in which circulating IgG autoantibodies directed against type XVII collagen (COL17) leads to skin blister formation. Interestingly, due to significant interspecies differences in its amino acid sequences in major pathogenic epitope on COL17, passive transfer of auto-antibodies (Abs) from patients with bullous pemphigoid into mice failed to induce blister formation. To overcome this species' differences, we have recently established a novel molecular method "humanization of autoantigen" by genetic manipulation. Using COL17-humanized mice, we have established 2 different mouse models of bullous pemphigoid. One is by injecting human auto-Abs from bullous pemphigoid patients into the neonatal COL17-humanized mice. Another model was induced by mouse Abs to human COL17 passively transferred from mother via placenta and milk into the neonatal COL17-humanized mice. "Humanization of autoantigen" is a novel and potential method to produce animal models for autoimmune diseases.

Novel animal models for bullous pemphigoid utilized by "humanization of autoantigen"