論文

査読有り
2011年7月

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

JOURNAL OF DERMATOLOGICAL SCIENCE
  • Tsuyoshi Hata
  • ,
  • Koji Nishifuji
  • ,
  • Kouji Shimoda
  • ,
  • Takashi Sasaki
  • ,
  • Taketo Yamada
  • ,
  • Takeji Nishikawa
  • ,
  • Shigeo Koyasu
  • ,
  • Masayuki Amagai

63
1
開始ページ
33
終了ページ
39
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jdermsci.2011.04.010
出版者・発行元
ELSEVIER IRELAND LTD

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)Dsg(3-/-) 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. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1016/j.jdermsci.2011.04.010
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000291846500005&DestApp=WOS_CPL

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