Examination of Msh6- and Msh3-deficient mice in class switching reveals overlapping and distinct roles of MutS homologues in antibody diversification.
Examination of Msh6- and Msh3-deficient mice in class switching reveals overlapping and distinct roles of MutS homologues in antibody diversification.
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在类切换中检查MSH6-和MSH3缺陷型小鼠，发现MUTS同源物在抗体多样化中的重叠和不同的作用。
DOI：
10.1084/jem.20040355
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发表时间：
2004-07-05
期刊：
影响因子：
--
通讯作者：
Scharff MD
中科院分区：
文献类型：
--
作者：
Li Z;Scherer SJ;Ronai D;Iglesias-Ussel MD;Peled JU;Bardwell PD;Zhuang M;Lee K;Martin A;Edelmann W;Scharff MD
体细胞高频突变和类别转换重组（CSR）有助于抗体的体细胞多样化。已表明MutS同源物（Msh）6（与Msh2协同）而非Msh3参与体细胞高频突变中A/T碱基替换的产生。然而，它们在CSR中的作用尚未见报道。在此我们表明Msh6 - / - 小鼠的CSR降低，而Msh3 - / - 小鼠则没有。当对转换区进行突变分析时，Msh6的缺失与G/C碱基对的转换突变增加、RGYW/WRCY热点处的突变以及G/C碱基靶向性的小幅增加有关。此外，Msh6 - / - 小鼠在Sγ3中表现出重组位点对GAGCT/GGGGT共有重复序列和热点的靶向性增加，但在Sμ中没有。与Msh2 - / - 小鼠相反，令人惊讶的是Msh6的缺失并没有改变Sμ - Sγ3转换连接点的特征。然而，Msh6 - / - 小鼠在Sμ和Sγ3连接点的定位上有所改变。尽管在Msh3 - / - 小鼠中没有观察到这些变化，但它们在转换连接点中有更高比例的大片段插入。总之，我们的数据表明MutS同源物Msh2、Msh3和Msh6在抗体多样化过程中发挥着重叠且不同的作用。
Somatic hypermutation and class switch recombination (CSR) contribute to the somatic diversification of antibodies. It has been shown that MutS homologue (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base substitutions in somatic hypermutation. However, their roles in CSR have not yet been reported. Here we show that Msh6 − / − mice have a decrease in CSR, whereas Msh3 − / − mice do not. When switch regions were analyzed for mutations, deficiency in Msh6 was associated with an increase in transition mutations at G/C basepairs, mutations at RGYW/WRCY hotspots, and a small increase in the targeting of G/C bases. In addition, Msh6 − / − mice exhibited an increase in the targeting of recombination sites to GAGCT/GGGGT consensus repeats and hotspots in Sγ3 but not in Sμ. In contrast to Msh2 − / − mice, deficiency in Msh6 surprisingly did not change the characteristics of Sμ-Sγ3 switch junctions. However, Msh6 − / − mice exhibited a change in the positioning of Sμ and Sγ3 junctions. Although none of these changes were seen in Msh3 − / − mice, they had a higher percentage of large inserts in their switch junctions. Together, our data suggest that MutS homologues Msh2, Msh3, and Msh6 play overlapping and distinct roles during antibody diversification processes.
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影响因子：
30.5
作者：
Manis, JP;Morales, JC;Carpenter, PB
通讯作者：
Carpenter, PB
影响因子：
32.4
作者：
Min, IM;Schrader, CE;Selsing, E
通讯作者：
Selsing, E
影响因子：
15.3
作者：
Faili, A;Aoufouchi, S;Weill, JC
通讯作者：
Weill, JC
DOI：
10.1073/pnas.241525998
发表时间：
2001-12-04
影响因子：
11.1
作者：
Ehrenstein, MR;Rada, C;Neuberger, MS
通讯作者：
Neuberger, MS
影响因子：
4.8
作者：
Genschel, J;Bazemore, LR;Modrich, P
通讯作者：
Modrich, P