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首页> 外文期刊>Journal of dermatological science >Transgenic rescue of desmoglein 3 null mice with desmoglein 1 to develop a syngeneic mouse model for pemphigus vulgaris.
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Transgenic rescue of desmoglein 3 null mice with desmoglein 1 to develop a syngeneic mouse model for pemphigus vulgaris.

机译：用desmoglein 1进行desmoglein 3无效小鼠的转基因拯救，以开发寻常型天疱疮的同系小鼠模型。

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BACKGROUND: An active disease mouse model of pemphigus vulgaris (PV) was developed using the adoptive transfer of splenocytes from Dsg3(-/-) mice with a mixed C57BL/6J (B6) and 129/Sv genetic background into B6-Rag2(-/-) mice. Further immunological investigation is needed to resolve the genetic mismatch between host and recipient mice. The B6-Dsg3(-/-) mice did not grow old enough to provide splenocytes, probably due to severe oral erosions, with resulting inhibition of food intake. OBJECTIVE: To rescue the B6-Dsg3(-/-) mice and to produce syngeneic PV model mice. METHODS: Transgenic expression of mouse Dsg1 was attempted to compensate for the genetic loss of Dsg3 using the keratin 5 promoter. We evaluated the compensatory ability of Dsg1 in vivo by comparing Dsg1(wt/wt), Dsg1(tg/wt), and Dsg1(tg/tg) mice. We generated a PV model via the adoptive transfer of B6-Dsg1(tg/tg)Dsg3(-/-) splenocytes to B6-Rag2(-/-) mice. RESULTS: Dsg1(tg/tg) and Dsg1(tg/wt) mice expressed ectopic Dsg1 on keratinocyte cell surfaces in the lower layers of the epidermis, oral epithelium, and telogen hair follicles. Ectopic Dsg1 blocked the pathogenic effects of AK23 anti-Dsg3 mAb, and improved the body weight loss, telogen hair loss, and survival rate dose-dependently. While the B6-Dsg1(wt/wt)Dsg3(-/-) mice died by week 2, over 80% of the B6-Dsg1(tg/tg)Dsg3(-/-) mice survived at week 6. Furthermore, the syngeneic PV model mice showed the characteristic phenotype, including stable anti-Dsg3 antibody production and suprabasilar acantholysis on histology. CONCLUSION: Transgenic expression of Dsg1 rescued the severe B6-Dsg3(-/-) phenotype and provided a syngeneic mouse model of PV, which may be a valuable tool for clarifying immunological mechanisms in autoimmunity and tolerance of Dsg3.
机译：背景：利用混合C57BL / 6J（B6）和129 / Sv遗传背景的Dsg3（-/-）小鼠脾细胞过继转移到B6-Rag2（-）中，建立了寻常性天疱疮（PV）活动性疾病小鼠模型。 /-） 老鼠。需要进一步的免疫学研究来解决宿主和受体小鼠之间的遗传失配。 B6-Dsg3（-/-）小鼠的年龄不足以提供脾细胞，这可能是由于严重的口腔糜烂所致，导致食物摄入受到抑制。目的：拯救B6-Dsg3（-/-）小鼠并产生同系PV模型小鼠。方法：尝试使用角蛋白5启动子通过转基因表达小鼠Dsg1来补偿Dsg3的遗传损失。我们通过比较Dsg1（wt / wt），Dsg1（tg / wt）和Dsg1（tg / tg）小鼠评估了Dsg1在体内的补偿能力。我们通过将B6-Dsg1（tg / tg）Dsg3（-/-）脾细胞过继转移至B6-Rag2（-/-）小鼠生成了PV模型。结果：Dsg1（tg / tg）和Dsg1（tg / wt）小鼠在表皮，口腔上皮和毛发生长的毛囊下层的角质形成细胞表面上表达异位Dsg1。异位Dsg1阻断AK23抗Dsg3 mAb的致病作用，并剂量依赖性地改善体重减轻，端粒丢失和成活率。尽管B6-Dsg1（wt / wt）Dsg3（-/-）小鼠在第2周时死亡，但超过80％的B6-Dsg1（tg / tg）Dsg3（-/-）小鼠在第6周存活。同基因PV模型小鼠表现出特征表型，包括稳定的抗Dsg3抗体产生和组织学上睑板棘皮松解。结论：Dsg1的转基因表达挽救了严重的B6-Dsg3（-/-）表型，并提供了PV的同基因小鼠模型，这可能是阐明Dsg3自身免疫和耐受性免疫机制的有价值的工具。

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