The Role of the Ets2 Transcription Factor in the Proliferation, Maturation, and Survival of Mouse Thymocytes1
The Role of the Ets2 Transcription Factor in the Proliferation, Maturation, and Survival of Mouse Thymocytes1
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Ets2 转录因子在小鼠胸腺细胞增殖、成熟和存活中的作用1
作者：
A. Zaldumbide;F. Carlotti;P. Pognonec;K. Boulukos
在这项研究中，我们通过建立在胸腺中特异性表达Ets 2或Ets 2显性阴性形式Δ ets 2的转基因小鼠，研究Ets 2表达对胸腺细胞增殖、成熟和存活的影响。我们发现，在年幼的动物中，与野生型同窝小鼠相比，Δ ets 2转基因胸腺中的T细胞较少，并且这些T细胞的成熟在CD 4 − CD 8 −双阴性向CD 4 + CD 8+双阳性转变时受到影响。随着Δ ets 2转基因动物年龄的增加，胸腺细胞数量的部分恢复和完全T细胞成熟恢复。然而，离体培养的成年Δ ets 2转基因小鼠的胸腺细胞对细胞死亡和糖皮质激素诱导的细胞凋亡比对照同窝小鼠的T细胞更敏感。我们还发现，成年ets 2转基因小鼠的T细胞增殖速度比野生型同窝出生的小鼠快。这些T细胞的增殖和存活明显受到细胞凋亡信号的影响：糖皮质激素诱导的细胞凋亡诱导ets 2转基因小鼠的T细胞在体内继续增殖，并且比对照同窝出生小鼠的T细胞在体外存活得更好。已经表明，c-Myc表达是胸腺增殖所需的，并改善地塞米松处理动物的胸腺细胞存活。我们发现，表达c-Myc，Ets 2的目标，是升高的T细胞新鲜分离的胸腺与地塞米松预处理的ets 2转基因小鼠。总之，这些结果表明Ets 2在胸腺细胞的增殖和存活中起作用，暗示Myc依赖性途径。
In this study, we investigated the effects of Ets2 expression on the proliferation, maturation, and survival of thymocytes by establishing transgenic mice that specifically express Ets2 or a dominant negative form of Ets2, Δets2, in the thymus. We show that, in young animals, there are fewer T cells in Δets2 transgenic thymi and that the maturation of these T cells is affected at the CD4−CD8− double-negative to CD4+CD8+ double-positive transition compared with wild-type littermate mice. Partial recovery in the number of thymocytes and full T cell maturation are restored with increasing age of Δets2 transgenic animals. However, thymocytes from adult Δets2 transgenic mice cultured ex vivo are more sensitive to cell death and to glucocorticoid-induced apoptosis than are T cells from control littermate mice. We also show that T cells from adult ets2 transgenic mice proliferate faster than their wild-type littermates. The proliferation and survival of these T cells are clearly affected upon apoptotic signals: glucocorticoid-induced apoptosis induces T cells from ets2 transgenic mice to continue to proliferate in vivo and to survive better ex vivo than T cells from control littermates. It has been shown that c-Myc expression is required for thymic proliferation and improves thymocyte survival of dexamethasone-treated animals. We show that the expression of c-Myc, an Ets2 target, is elevated in T cells freshly isolated from thymi of ets2 transgenic mice pretreated with dexamethasone. Together, these results show that Ets2 plays a role in the proliferation and survival of thymocytes, implicating a Myc-dependent pathway.
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ets 基因在小鼠胸腺细胞亚群和 T 细胞中的表达。
DOI：
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发表时间：
1989
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bhat,NK;Komschlies,KL;Fujiwara,S;Fisher,RJ;Mathieson,BJ;Gregorio,TA;Young,HA;Kasik,JW;Ozato,K;Papas,TS
通讯作者：
Papas,TS
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
通过 ets 家族蛋白和 E2F-1 靶向的单个 DNA 结合位点双重控制 myc 表达。
影响因子：
8
作者：
Roussel,MF;Davis,JN;Cleveland,JL;Ghysdael,J;Hiebert,SW
通讯作者：
Hiebert,SW
未成熟胸腺细胞中的皮质类固醇靶向 NF-kappa B/c-myc 依赖性生存途径。
DOI：
--
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wang,W;Wykrzykowska,J;Johnson,T;Sen,R;Sen,J
通讯作者：
Sen,J
小鼠 bcl-x 基因的基因组组织、启动子区域分析和染色体定位。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Grillot,DA;Gonzalez-Garcia,M;Ekhterae,D;Duan,L;Inohara,N;Ohta,S;Seldin,MF;Nunez,G
通讯作者：
Nunez,G