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

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

    研究成果: ジャーナルへの寄稿記事

    抄録

    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

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    Chondroma
    Chondrocytes
    Cartilage
    T-Lymphocytes
    Hyperplasia
    Osteochondroma
    Adoptive Transfer
    Extracellular Signal-Regulated MAP Kinases
    Cell Lineage
    Bone Marrow Cells
    Fluorescence
    Alleles
    Phenotype
    Growth
    Genes

    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

    Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice. / Shiokawa, Moe; Lu, Xiuyuan; Miyake, Yasunobu; Ishikawa, Eri; Pagès, Gilles; Pouysségur, Jacques; Ogata, Masato; Yamasaki, Shou.

    :: International Immunology, 巻 29, 番号 10, 01.10.2017, p. 479-485.

    研究成果: ジャーナルへの寄稿記事

    Shiokawa, M, Lu, X, Miyake, Y, Ishikawa, E, Pagès, G, Pouysségur, J, Ogata, M & Yamasaki, S 2017, 'Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice', International Immunology, 巻. 29, 番号 10, pp. 479-485. https://doi.org/10.1093/intimm/dxx056
    Shiokawa M, Lu X, Miyake Y, Ishikawa E, Pagès G, Pouysségur J その他. Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice. International Immunology. 2017 10 1;29(10):479-485. https://doi.org/10.1093/intimm/dxx056
    Shiokawa, Moe ; Lu, Xiuyuan ; Miyake, Yasunobu ; Ishikawa, Eri ; Pagès, Gilles ; Pouysségur, Jacques ; Ogata, Masato ; Yamasaki, Shou. / Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice. :: International Immunology. 2017 ; 巻 29, 番号 10. pp. 479-485.
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    abstract = "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.",
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    AU - Shiokawa, Moe

    AU - Lu, Xiuyuan

    AU - Miyake, Yasunobu

    AU - Ishikawa, Eri

    AU - Pagès, Gilles

    AU - Pouysségur, Jacques

    AU - Ogata, Masato

    AU - Yamasaki, Shou

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