title: Transgenic rescue of desmoglein 3 null mice with desmoglein 1 to develop a syngeneic mouse model for pemphigus vulgaris.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors: Tsuyoshi
authors: T
authors: Hata
authors: Koji
authors: K
authors: Nishifuji
authors: Kouji
authors: K
authors: Shimoda
authors: Takashi
authors: T
authors: Sasaki
authors: Taketo
authors: T
authors: Yamada
authors: Takeji
authors: T
authors: Nishikawa
authors: Shigeo
authors: S
authors: Koyasu
authors: Masayuki
authors: M
authors: Amagai