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Ankylosing enthesitis associated with up-regulated IFN-γ and IL-17 production in (BXSB × NZB) F1 male mice: a new mouse model

  • Original Article
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Modern Rheumatology

Abstract

We found that in contrast to (BXSB × NZB) F1 female mice that spontaneously develop severe systemic lupus erythematosus (SLE), male (BXSB × NZB) F1 mice are not prone to SLE, but instead develop seronegative ankylosing enthesitis in ankle/tarsal joints only when caged in groups, with the incidence reaching 83% at 7 months of age. This ankylosis is microscopically characterized by a marked proliferation of fibroblast-like cells positive for bone morphogenetic protein (BMP)-2 in association with heterotropic formation of cartilages and bones in hyperplastic entheseal tissues and subsequent fusion of tarsal bones. Elevated potentials of popliteal lymph node T cells producing interleukin (IL)-17 and interferon (IFN)-γ were significantly associated with joint ankylosis, suggesting the involvement of these cytokines in effector phase mechanisms of the disease, including up-regulated BMP signaling pathways. There was no difference in serum autoantibody levels between affected and unaffected mice. Parental BXSB and NZB strains of both sexes did not develop the disease even when caged in groups, indicating that the disease develops under the control of susceptibility genes derived from both parental strains. These results indicate that (BXSB × NZB) F1 male mice are a suitable model for clarifying genetic, environmental and molecular mechanisms underlying ankylosing enthesitis and related diseases.

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Acknowledgments

We thank Michiko Yamada (National Research Institute for Child Health and Development) for skillful assistance of cytokine analysis, and Masato Nose (Ehime University Graduate School of Medicine, Ehime, Japan) and Masao Ono (Tohoku University Graduate School of Medicine, Sendai, Japan) for helpful discussion. This study was supported by Grant-in-Aid for Scientific Research on Priority Areas (project no. 13140205) from the Ministry of Education, Science, Technology, Sports and Culture of Japan, and Grant for Research on Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Department of Pharmacy, Kanazawa Medical Center, National Hospital Organization, Kanazawa, Ishikawa, Japan

    Yasuharu Abe

  2. Department of Immunology, Tokyo Medical University, Tokyo, Japan

    Yasuharu Abe

  3. Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Mareki Ohtsuji, Naomi Ohtsuji, Qingshun Lin, Hiromichi Tsurui, Toshikazu Shirai & Sachiko Hirose

  4. Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan

    Susumu Nakae

  5. Frontier Research Initiative, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Susumu Nakae

  6. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan

    Susumu Nakae

  7. Animal Research Center, Tokyo Medical University, Tokyo, Japan

    Katsuko Sudo

Authors
  1. Yasuharu Abe
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  2. Mareki Ohtsuji
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  3. Naomi Ohtsuji
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  6. Susumu Nakae
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  7. Toshikazu Shirai
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  8. Katsuko Sudo
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  9. Sachiko Hirose
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Correspondence to Sachiko Hirose.

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Abe, Y., Ohtsuji, M., Ohtsuji, N. et al. Ankylosing enthesitis associated with up-regulated IFN-γ and IL-17 production in (BXSB × NZB) F1 male mice: a new mouse model. Mod Rheumatol 19, 316–322 (2009). https://doi.org/10.1007/s10165-009-0166-0

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  • DOI: https://doi.org/10.1007/s10165-009-0166-0

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