Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice

Moe Shiokawa, Xiuyuan Lu, Yasunobu Miyake, Eri Ishikawa, Gilles Pagès, Jacques Pouysségur, Masato Ogata, Sho Yamasaki

    研究成果: ジャーナルへの寄稿記事

    抜粋

    Lineage-specific Cre Tg mice are widely used to delineate the functions of genes in a tissue-specific manner. Several T-cell-specific promoter cassettes have been developed; however, the activities of those promoters in non-T cells have not been investigated extensively. Here, we report that CD2-Cre-mediated deletion of Erk proteins by generating CD2-Cre × Erk1-/-Erk2flox/flox (ErkΔCD2-Cre) mice results in abnormal cartilage hyperplasia. Histological analysis revealed that this abnormality is caused by aberrant hyperplasia of chondrocytes. The presence of Erk-deficient T cells is not required for this chondroma formation, as it was similarly observed in the absence of T cells in a CD3e-deficient background. In addition, adoptive transfer of bone marrow cells from ErkΔCD2-Cre mice to wild-type recipients did not cause chondroma formation, suggesting that Erk-deficient non-immune cells are responsible for this abnormality. By tracing Cre-expressed tissues using a ROSA26-STOP-RFP allele, we found that the chondroma emitted RFP fluorescence, indicating that functional Cre is expressed in hyperplastic chondrocytes in ErkΔCD2-Cre mice. Furthermore, RFP+ chondrocytes were also found in an Erk-sufficient background, albeit without aberrant growth. These results suggest that unexpected expression of CD2- driven Cre in chondrocytes generates Erk-deficient chondrocytes, resulting in hyperplastic cartilage formation. Recently, two independent reports showed that CD4-Cre-mediated Ras-Erk signaling ablation led to similar abnormal cartilage formation (Guittard, G., Gallardo, D. L., Li, W. et al. 2017. Unexpected cartilage phenotype in CD4-Cre-conditional SOS-deficient mice. Front. Immunol. 8:343; Wehenkel, M., Corr, M., Guy, C. S. et al. 2017. Extracellular signal-regulated kinase signaling in CD4-expressing cells inhibits osteochondromas. Front. Immunol. 8:482). Together with these reports, our study suggests that an unexpected link exists between T-like cell and chondrocyte lineages during ontogeny.

    元の言語英語
    ページ(範囲)479-485
    ページ数7
    ジャーナルInternational immunology
    29
    発行部数10
    DOI
    出版物ステータス出版済み - 10 1 2017

      フィンガープリント

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    これを引用

    Shiokawa, M., Lu, X., Miyake, Y., Ishikawa, E., Pagès, G., Pouysségur, J., ... Yamasaki, S. (2017). Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice. International immunology, 29(10), 479-485. https://doi.org/10.1093/intimm/dxx056