KRN/I-Ag7 Mouse Arthritis Is Independent of Complement C3

  • Patricia Y. Tsao
  • Vaishali Arora
  • Mei Qing Ji
  • Alexander C. Wright
  • Robert A. Eisenberg



KRN/I-Ag7 (KxB/N) is a mouse model of inflammatory arthritis, which resembles human rheumatoid arthritis. Arthritis in these animals is caused by autoreactivity to a ubiquitously expressed autoantigen, glucose-6 phosphate isomerase. Tolerance is broken at both the T cell and B cell level. The sera from KRN/I-Ag7 mice can induce mouse arthritis in healthy mice. Complement components of the alternative complement pathway, including C3, have been shown to be required in induction of mouse arthritis by serum transfer.


We have bred KRN/I-Ag7 mice onto a C3-deficient background and followed cohorts for the spontaneous appearance of arthritis. We have also transferred KxB/N serum to B6.I-A g7 recipients.


C3-deficient KRN/I-Ag7 mice spontaneously developed severe, destructive arthritis, comparable to that seen in C3-intact KRN/I-Ag7 mice. However, serum transfer experiments confirmed the strong requirement for C3 in the passive model.


The pathogenesis of spontaneous KRN/I-Ag7 arthritis can largely proceed by complement-independent pathways and must have pathology effector mechanisms in addition to those seen in the passive serum transfer model.


Arthritis autoantibody KRN GPI complement C3 



We thank Dr. Diane Mathis for the generous sharing of mice, constructs, and protocols. This study was supported by the Arthritis Foundation, the American Autoimmune Related Disease Association, Bracco Research USA, the NIH (R01-AR-34156; R01-AI063626) and the Small Animal Imaging Facility, Department of Radiology, University of Pennsylvania.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Patricia Y. Tsao
    • 1
  • Vaishali Arora
    • 1
  • Mei Qing Ji
    • 1
  • Alexander C. Wright
    • 2
  • Robert A. Eisenberg
    • 1
  1. 1.Department of Medicine, Division of RheumatologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of RadiologyUniversity of Pennsylvania Medical CenterPhiladelphiaUSA

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