Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice
Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice
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DOI：
10.1073/pnas.0237043100
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发表时间：
2003-02-04
影响因子：
11.1
通讯作者：
Oettinger, MA
中科院分区：
文献类型：
--
作者：
Akamatsu, Y;Monroe, R;Oettinger, MA
重组激活基因（RAG）1和RAG 2蛋白包含V（D）J重组酶的淋巴细胞特异性组分，并且是抗原受体可变区基因组装所需的。缺少C-末端144个氨基酸的突变截短RAG 2蛋白（“核心”RAG 2）与核心RAG 1一起能够介导体外和转染细胞系中V（D）J重组所需的基本生物化学步骤。在这里，我们研究了用核心RAG 2替换小鼠中的内源性RAG 2基因座的效果。这些小鼠产生大量的B和T细胞，证明核心RAG 2蛋白保留了显著的体内功能。然而，核心RAG 2小鼠显示B和T细胞总数减少，反映了与染色体V（D）J重组减少相关的祖细胞阶段淋巴细胞发育受损。我们讨论了潜在的作用RAG 2的C末端介导的内源性抗原受体位点的重排。
The recombination-activating gene (RAG)l and RAG2 proteins comprise the lymphocyte-specific components of the V(D)J recombinase and are required for the assembly of antigen-receptor variable-region genes. A mutant truncated RAG2 protein ("core" RAG2) lacking the C-terminal 144 amino acids, together with core RAG1, is able to mediate the basic biochemical steps required for V(D)J recombination in vitro and in transfected cell lines. Here we examine the effect of replacing the endogenous RAG2 locus in mice with core RAG2. These mice generate substantial numbers of B and T cells, demonstrating that the core RAG2 protein retains significant in vivo function. However, core RAG2 mice display a reduction in the total number of B and T cells, reflecting impaired lymphocyte development at the progenitor stage associated with reduced chromosomal V(D)J recombination. We discuss potential roles of the RAG2 C terminus in mediating rearrangement of endogenous antigen-receptor loci.