Nishie Wataru, Shimizu Hiroshi
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Nihon Rinsho Meneki Gakkai Kaishi. 2009 Dec;32(6):472-7. doi: 10.2177/jsci.32.472.
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.
人类疾病的动物模型对于更好地理解其发病机制以及开发新疗法非常有用。然而，由于不同物种之间存在差异，有时很难在动物身上重现可靠的疾病表型。大疱性类天疱疮是最常见的自身免疫性水疱性皮肤病，其中针对 XVII 型胶原蛋白（COL17）的循环 IgG 自身抗体导致皮肤水疱形成。有趣的是，由于 COL17 主要致病表位的氨基酸序列存在显著的种间差异，将大疱性类天疱疮患者的自身抗体（Abs）被动转移到小鼠体内未能诱导水疱形成。为了克服这种物种差异，我们最近通过基因操作建立了一种新的分子方法“自身抗原人源化”。利用 COL17 人源化小鼠，我们建立了 2 种不同的大疱性类天疱疮小鼠模型。一种是将大疱性类天疱疮患者的人源自身抗体注射到新生的 COL17 人源化小鼠体内。另一种模型是通过母体经胎盘和乳汁将小鼠抗人 COL17 抗体被动转移到新生的 COL17 人源化小鼠体内诱导产生的。“自身抗原人源化”是一种用于制备自身免疫性疾病动物模型的新颖且有潜力的方法。
