Transgenic rescue of desmoglein 3 null mice with desmoglein 1 to develop a syngeneic mouse model for pemphigus vulgaris

Tsuyoshi Hata, Koji Nishifuji, Kouji Shimoda, Takashi Sasaki, Taketo Yamada, Takeji Nishikawa, Shigeo Koyasu, Masayuki Amagai

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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 Dsg1wt/wt, Dsg1tg/wt, and Dsg1tg/tg mice. We generated a PV model via the adoptive transfer of B6-Dsg1tg/tgDsg3-/- splenocytes to B6-Rag2-/- mice. Results: Dsg1tg/tg and Dsg1tg/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-Dsg1wt/wtDsg3-/- mice died by week 2, over 80% of the B6-Dsg1tg/tgDsg3-/- 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.

Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalJournal of Dermatological Science
Issue number1
Publication statusPublished - 2011 Jul


  • Autoantibody
  • Autoimmunity
  • Cadherin
  • Mouse model

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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