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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A mutation in a chromosome condensin II subunit, kleisin β, specifically disrupts T cell development
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A mutation in a chromosome condensin II subunit, kleisin β, specifically disrupts T cell development

机译：染色体凝缩蛋白II亚基kleisinβ中的突变可特异性破坏T细胞发育

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摘要

Condensins are ubiquitously expressed multiprotein complexes that are important for chromosome condensation and epigenetic regulation of gene transcription, but whose specific roles in vertebrates are poorly understood. We describe a mouse strain, nessy, isolated during an ethylnitrosourea screen for recessive immunological mutations. The nessy mouse has a defect in T lymphocyte development that decreases circulating T cell numbers, increases their expression of the activation/memory marker CD44, and dramatically decreases the numbers of CD4~+CD8~+ thymocytes and their immediate DN4 precursors. A missense mutation in an unusual alternatively spliced first exon of the kleisin β gene, a member of the condensin II complex, was shown to be responsible and act in a T cell-autonomous manner. Despite the ubiquitous expression and role of condensins, kleisin β~(neses) mice were viable, fertile, and showed no defects even in the parallel pathway of B cell lymphocyte differentiation. These data define a unique lineage-specific requirement for kleisin β in mammalian T cell differentiation.
机译：凝缩蛋白是普遍表达的多蛋白复合物，对于染色体凝缩和基因转录的表观遗传调控很重要，但是人们对其在脊椎动物中的特殊作用知之甚少。我们描述了在隐性免疫突变的乙基亚硝基脲筛选过程中分离出的小鼠菌株，nessy。这只小老鼠的T淋巴细胞发育有缺陷，可减少循环T细胞数量，增加其激活/记忆标记CD44的表达，并显着减少CD4〜+ CD8〜+胸腺细胞及其直接DN4前体的数量。 kleisinβ基因的一个不寻常的选择性剪接的第一个外显子（condensin II复合体的一个成员）中的错义突变被证明是负责的，并且以T细胞自主的方式起作用。尽管浓缩素的表达和作用无处不在，但kleisinβ〜（nes / nes）小鼠仍是活的，可育的，甚至在B细胞淋巴细胞分化的平行途径中也没有缺陷。这些数据定义了哺乳动物T细胞分化中对kleisinβ独特的谱系特异性要求。

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