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The SKG Mutation in ZAP-70 also Confers Arthritis Susceptibility in C57 Black Mouse Strains.
Guerard, S; Boieri, M; Hultqvist, M; Holmdahl, R; Wing, K.
Afiliación
  • Guerard S; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Boieri M; Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Hultqvist M; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Holmdahl R; Redoxis AB, Medicon Village Scheelevägen 2, Lund, Sweden.
  • Wing K; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Scand J Immunol ; 84(1): 3-11, 2016 Jul.
Article en En | MEDLINE | ID: mdl-27040161
Various rodent models of arthritis are essential to dissect the full complexity of human rheumatoid arthritis (RA), a common autoimmune disease affecting joints. The SKG model of arthritis originates from a spontaneous mutation in ZAP-70 found in a BALB/c colony. This mutation affects T cell selection due to reduced TCR signalling, which allows leakage of self-reactive T cells from the thymus. To further expand the practical applicability of this unique model in arthritis research, we investigated the arthritogenicity of the SKG mutation in two common black mouse strains C57BL/6.Q and C57BL/10.Q and compared to BALB/c.Q. Mice retained the reduced TCR signalling characteristic of SKG.BALB/c mice, which leads to similar alteration in thymic selection. Importantly, mice also retained susceptibility to chronic arthritis after a single injection of mannan from Saccharomyces cerevisiae, with comparable prevalence and severity regardless of the genetic background. Further characterization of CD4(+) T cells revealed a similar bias towards IL-17 production and activated T cell phenotype in all SKG strains compared to respective wild type controls. Finally, transfer of SKG thymocytes conferred susceptibility to recipients, which confirm the intrinsic defect and pathogenicity of T cells. Overall, these results underline the strong impact that the W163C ZAP-70 mutation has on T cell-driven arthritis, and they support the use of the SKG model in black mice, which is useful for further investigations of this distinctive arthritis model to better understand autoimmunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Proteína Tirosina Quinasa ZAP-70 / Células Th17 / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Scand J Immunol Año: 2016 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Proteína Tirosina Quinasa ZAP-70 / Células Th17 / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Scand J Immunol Año: 2016 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido