Transgenic rescue of desmoglein 3 null mice with desmoglein 1 to develop a syngeneic mouse model for pemphigus vulgaris
Journal of Dermatological Science(2011)
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 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.
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Key words
PV,Dsg,Ab,K5
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