Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice
Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice
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CD2-Cre 驱动的 Erk 缺陷小鼠自发软骨瘤形成
DOI：
10.1093/intimm/dxx056
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发表时间：
2017
影响因子：
4.4
通讯作者：
Yamasaki Sho
中科院分区：
文献类型：
--
作者：
Shiokawa Moe;Lu Xiuyuan;Miyake Yasunobu;Ishikawa Eri;Pages Gilles;Pouyssegur Jacques;Ogata Masato;Yamasaki Sho
谱系特异性Cre - Tg小鼠被广泛用于以组织特异性方式描述基因的功能。已经开发了几种t细胞特异性启动子磁带；然而，这些启动子在非t细胞中的活性尚未得到广泛研究。在这里，我们报告了CD2-Cre介导的Erk蛋白缺失，通过生成CD2-Cre × Erk1 - / - erk2flox /flox（Erk∆CD2-Cre）小鼠导致软骨异常增生。组织学分析显示这种异常是由软骨细胞异常增生引起的。这种软骨瘤的形成并不需要erk缺陷T细胞的存在，因为在cd3ε缺陷背景下缺乏T细胞时也观察到类似的情况。此外，将Erk∆CD2-Cremice的骨髓细胞过继移植给野生型受体，并未导致软骨瘤的形成，这表明Erk缺陷的非免疫细胞是导致这种异常的原因。利用ROSA26-STOP-RFP等位基因追踪Cre表达组织，我们发现软骨瘤发出RFP荧光，表明Erk∆CD2-Cremice的增生软骨细胞中表达功能性Cre。此外，在erk充足的背景下，RFP+软骨细胞也被发现，尽管没有异常生长。这些结果表明，在软骨细胞中意外表达cd2驱动的Cre会产生erk缺陷的软骨细胞，导致软骨增生形成。最近，两份独立报告显示，cd4 - cre介导的Ras-Erk信号消融导致类似的软骨异常形成（Guittard， G., Gallardo， D. L, Li， W.et al. 2017）。cd4 - cre条件下sos缺陷小鼠的意外软骨表型。Immunol 8:343;Wehenkel， M., Corr， M., Guy， C. s .等。2017。细胞外信号调节的激酶信号在表达cd4的细胞中抑制骨软骨瘤。Immunol 8:482)。结合这些报道，我们的研究表明，在个体发育过程中，t样细胞和软骨细胞谱系之间存在着意想不到的联系。
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(Erk∆CD2-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 CD3ε-deficient background. In addition, adoptive transfer of bone marrow cells from Erk∆CD2-Cremice 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 Erk∆CD2-Cremice. 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.