The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development
The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development
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DOI：
10.1016/s1074-7613(02)00448-x
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发表时间：
2002-11-01
期刊：
影响因子：
32.4
通讯作者：
Schlissel, MS
中科院分区：
文献类型：
--
作者：
Liang, HE;Hsu, LY;Schlissel, MS
先前的体外研究确定了V（D）J重组所必需的RAG 1和RAG 2的最小区域。为了表征RAG 2的C-末端“C”部分的作用，我们产生核心-RAG 2敲入小鼠。我们发现，核心RAG 2的重组酶复合物是选择性缺陷，在IgH和TCRO基因座催化V到DJ重排，导致部分发育阻滞在B和T淋巴细胞生成。重组中间体的分析表明，在反应的裂解阶段的缺陷。我们还观察到在核心RAG 2表达的胸腺细胞中整体重组酶活性的降低，这使我们认为缺陷重组酶与VH和Vbeta基因片段特有的RSS序列的相互作用可能是核心RAG 2小鼠中特异性V-to-DJ重排缺陷的基础。
Previous in vitro studies defined the minimal regions of RAG1 and RAG2 essential for V(D)J recombination. In order to characterize the role of the C-terminal "dispensable" portion of RAG2, we generated core-RAG2 knock-in mice. We found that the core-RAG2-containing recombinase complex is selectively defective in catalyzing V-to-DJ rearrangement at the IgH and TCRO loci, resulting in partial developmental blocks in B and T lymphopoiesis. Analysis of recombination intermediates showed defects at the cleavage phase of the reaction. We also observed a reduction in overall recombinase activity in core-RAG2-expressing thymocytes, leading us to suggest that the interaction of a defective recombinase with RSS sequences unique to VH and Vbeta gene segments may underlie the specific V-to-DJ rearrangement defect in core-RAG2 mice.