Thymocyte development in early growth response gene 1-deficient mice
Thymocyte development in early growth response gene 1-deficient mice
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DOI：
10.4049/jimmunol.169.4.1713
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发表时间：
2002-08-15
影响因子：
4.4
通讯作者：
Kersh, GJ
中科院分区：
文献类型：
--
作者：
Bettini, M;Xi, HK;Kersh, GJ
早期生长反应基因I（Egr 1）编码一个含有锌指DNA结合结构域的转录调节因子。Egr 1表达由多种细胞外刺激诱导，包括TCR-配体相互作用。它在胸腺中的表达模式和对ERK激活的依赖性导致了它在T细胞发育中起作用的推测，但这种作用的确切性质尚未确定。为了更清楚地定义Egr 1在胸腺细胞发育中的作用，我们分析了Egr 1缺陷小鼠的胸腺细胞。我们发现，Egr 1缺陷小鼠的胸腺含有的细胞是年龄匹配的对照组的两倍，胸腺细胞数量的增加在早期CD 4/CD 8双阴性发育阶段是明显的。随后成熟为CD 4/CD 8双阳性阶段和双阳性细胞的存活在Egr 1缺陷动物中均表现正常。我们还发现，Egr 1促进CD 4和CD 8单阳性细胞的正选择，而在负选择中不起主要作用。Egr 1通过增强螺旋-环-螺旋抑制剂Id 3和抗凋亡分子bcl-2的表达来影响阳性选择。因此，Egr 1在胸腺细胞发育的多个阶段将发育信号转化为基因表达的适当变化。
Early growth response gene I (Egr1) codes for a transcriptional regulator that contains a zinc-finger DNA binding domain. Egr1 expression is induced by a variety of extracellular stimuli including TCR-ligand interactions. Its pattern of expression in the thymus and dependence on ERK activation have led to speculation that it has a role in T cell development, but the exact nature of this role has been undefined. To more clearly define the role of Egr1 in thymocyte development, we have analyzed thymocytes from Egr1-deficient mice. We find that thymuses from Egr1-deficient mice contain twice as many cells as age-matched controls, and the increase in thymocyte number is apparent at the early CD4/CD8 double negative stage of development. Subsequent maturation to the CD4/CD8 double positive stage and survival of the double positive cells both appear normal in Egr1-deficient animals. We also find that Egr1 promotes positive selection of both CD4 and CD8 single positive cells without playing a major role in negative selection. Egr1 influences positive selection by enhancing expression of the helix-loop-helix inhibitor Id3 and the anti-apoptosis molecule bcl-2. Thus, Egr1 translates developmental signals into appropriate changes in gene expression at multiple stages of thymocyte development.