Transcription factor zinc finger and BTB domain 1 is essential for lymphocyte development.
Transcription factor zinc finger and BTB domain 1 is essential for lymphocyte development.
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DOI：
10.4049/jimmunol.1200623
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发表时间：
2012-08-01
期刊：
影响因子：
--
通讯作者：
Puck JM
中科院分区：
文献类型：
--
作者：
Punwani D;Simon K;Choi Y;Dutra A;Gonzalez-Espinosa D;Pak E;Naradikian M;Song CH;Zhang J;Bodine DM;Puck JM
在一个不相关项目的转基因小鼠的纯合子中意外地发现了 T 淋巴细胞的缺失。 T 细胞发育未超过双阴性 1 期胸腺细胞，导致胸腺细胞减少、退化。 B 细胞存在，但 NK 细胞数量和 B 细胞同种型转换减少。野生型造血细胞的移植纠正了这一缺陷，该缺陷可追溯到染色体 12C3 上转基因插入位点涉及 5 个连续基因的缺失。使用 BAC 转基因的补充表明锌指 BTB-POZ 结构域蛋白 1 (Zbtb1) 与免疫缺陷有关，证实了其在 T 细胞发育中的作用，并表明其参与 B 细胞和 NK 细胞分化。 Zbtb1 的靶向破坏重现了原始转基因动物的 T−B+NK− 严重联合免疫缺陷 (SCID) 表型。 Zbtb1 的敲除增加了骨髓造血干细胞的数量以及多能和早期淋巴谱系，这表明常见淋巴祖细胞存在分化瓶颈。编码Zbtb1（一种预测的转录抑制因子）的mRNA在造血干细胞、胸腺细胞和前B细胞中的表达量最大，凸显了其在淋巴发育中的重要作用。
Absent T lymphocytes were unexpectedly found in homozygotes of a transgenic mouse from an unrelated project. T cell development did not progress beyond double negative stage 1 thymocytes, resulting in a hypocellular, vestigial thymus. B cells were present, but NK cell number and B cell isotype switching were reduced. Transplantation of wild type hematopoietic cells corrected the defect, which was traced to a deletion involving 5 contiguous genes at the transgene insertion site on chromosome 12C3. Complementation using BAC transgenesis implicated zinc finger BTB-POZ domain protein 1 (Zbtb1) in the immunodeficiency, confirming its role in T cell development and suggesting involvement in B and NK cell differentiation. Targeted disruption of Zbtb1 recapitulated the T− B+ NK− severe combined immunodeficiency (SCID) phenotype of the original transgenic animal. Knockouts for Zbtb1 had expanded populations of bone marrow hematopoietic stem cells and also multipotent and early lymphoid lineages, suggesting a differentiation bottleneck for common lymphoid progenitors. Expression of mRNA encoding Zbtb1, a predicted transcription repressor, was greatest in hematopoietic stem cells, thymocytes and pre-B cells, highlighting its essential role in lymphoid development.
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影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
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影响因子：
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1.7
作者：
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通讯作者：
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