Impairment of T cell development in deltaEF1 mutant mice.
Impairment of T cell development in deltaEF1 mutant mice.
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DOI：
10.1084/jem.185.8.1467
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发表时间：
1997-04-21
期刊：
影响因子：
--
通讯作者：
Kondoh H
中科院分区：
文献类型：
--
作者：
Higashi Y;Moribe H;Takagi T;Sekido R;Kawakami K;Kikutani H;Kondoh H
采用小鼠胚胎干细胞基因打靶的方法，通过构建δ EF 1突变小鼠，在体内研究了锌指和同源结构域转录因子δ EF 1的调控功能。δ EF 1的突变等位基因产生的δ EF 1蛋白的截短形式缺少邻近COOH末端的锌指簇。δ EF 1纯合子突变小鼠胸腺发育不良，无皮质和髓质之分。突变胸腺细胞的分析表明，总细胞数减少了两个数量级，伴随着受损的胸腺细胞发育。早期胸腺内c-kit+ T前体细胞大量耗竭。随后的胸腺细胞发育似乎也受到影响，如CD 4或CD 8表达细胞的扭曲组成所评估的。突变小鼠胸腺细胞α4整合素表达增加，这可能与突变小鼠T细胞缺陷有关。在突变小鼠的外周淋巴结组织中，相对于CD 4 + CD 8 −单阳性细胞，CD 4 − CD 8+单阳性细胞显著减少。与T细胞相反，其他造血谱系似乎是正常的。这些数据表明，δ EF 1在多个阶段参与调节T细胞发育。
Using the method of gene targeting in mouse embryonic stem cells, regulatory function of δEF1, a zinc finger and homeodomain-containing transcription factor, was investigated in vivo by generating the δEF1 mutant mice. The mutated allele of δEF1 produced a truncated form of the δEF1 protein lacking a zinc finger cluster proximal to COOH terminus. The homozygous δEF1 mutant mice had poorly developed thymi with no distinction of cortex and medulla. Analysis of the mutant thymocyte showed reduction of the total cell number by two orders of magnitude accompanying the impaired thymocyte development. The early stage intrathymic c-kit+ T precursor cells were largely depleted. The following thymocyte development also seemed to be affected as assessed by the distorted composition of CD4- or CD8-expressing cells. The mutant thymocyte showed elevated α4 integrin expression, which might be related to the T cell defect in the mutant mice. In the peripheral lymph node tissue of the mutant mice, the CD4−CD8+ single positive cells were significantly reduced relative to CD4+CD8− single positive cells. In contrast to T cells, other hematopoietic lineages appeared to be normal. The data indicated that δEF1 is involved in regulation of T cell development at multiple stages.