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首页> 外文期刊>Molecular and Cellular Biology >Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice
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Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

机译：p51-Ets1亚型特异性空小鼠的胸腺肿大，微脾和外周淋巴细胞的稳态稳态增殖。

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Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1ΔVII (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1ΔVII isoform. Ets1ΔVII homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8+ and CD8+CD4+ thymocytes were observed. Lymphoid cell (CD19+, CD4+, and CD8+) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1ΔVII mutants demonstrate lymphocyte maturation defects associated with misregulation of p16Ink4a, p27Kip1, and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis.
机译：Ets1是Ets转录因子家族的成员。外显子VII的可变剪接产生两种天然存在的蛋白亚型：全长Ets1（p51-Ets1）和Ets1 ΔVII（p42-Ets1）。这些同工型在蛋白质-蛋白质相互作用，DNA结合动力学和转录靶标特异性方面具有关键区别。小鼠体内两种Ets1亚型的破坏均导致可检测的NK和NKT细胞活性丧失以及B和T淋巴细胞缺陷。我们生成了只表达Ets1 ΔVII同种型的小鼠。 Ets1 ΔVII纯合子小鼠不表达p51-Ets1，相对于野生型而言，p42-Ets1蛋白水平升高，并显示出围生期致死率，胸腺肿大和外周淋巴细胞减少。胸腺和脾脏中的增殖都增加，而胸腺中的凋亡减少，而纯合子的脾脏中的凋亡增加。观察到CD8 + 和CD8 + CD4 + 胸腺细胞显着升高。淋巴样细胞减少（CD19 + ，CD4 + 和CD8 + ）减少主要是脾细胞减少，记忆细胞减少和衰竭稳态增殖以维持外周淋巴细胞。总体而言，Ets1 ΔVII突变体表现出与p16 Ink4a ，p27 Kip1 和CD44的失调相关的淋巴细胞成熟缺陷。因此，Ets1亚型的差异调节的平衡代表了控制淋巴成熟和体内平衡的潜在机制。

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