XRCC3 loss leads to midgestational embryonic lethality in mice.
XRCC3 loss leads to midgestational embryonic lethality in mice.
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DOI：
10.1016/j.dnarep.2021.103227
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发表时间：
2021-12
期刊：
影响因子：
3.8
通讯作者：
Jasin M
中科院分区：
文献类型：
--
作者：
Prakash R;Freyer L;Saiz N;Gavrilov S;Wang RQ;Romanienko PJ;Lacy E;Hadjantonakis AK;Jasin M
RAD 51旁系同源物是同源重组（HR）机制的关键组分。已经报道了四种典型的RAD 51旁系同源物的小鼠突变体，并且这些突变体中的每一种都表现出胚胎致死性，尽管在不同的妊娠阶段。然而，缺乏第五个RAD 51基因片段XRCC 3的小鼠的表型尚未报道。在这里，我们报告说，Xrcc 3基因敲除小鼠表现出妊娠中期致死性，轻度表型开始于约E8.25，但严重的发育异常明显的E9.0-9.5。最明显的表型是小尺寸和胚胎未能转向胎儿位置。在步行者A盒中一个关键的ATP酶残基处的敲入突变导致在相似阶段的胚胎致死。敲除小鼠的死亡可以通过纯合或杂合Trp 53突变延迟几天，这与XRCC 3在促进基因组完整性方面的重要作用保持一致。鉴于XRCC 3是与RAD 51 C的两种RAD 51旁系同源复合物之一的独特成员，这些结果表明两种RAD 51旁系同源复合物都是小鼠发育所需的。
RAD51 paralogs are key components of the homologous recombination (HR) machinery. Mouse mutants have been reported for four of the canonical RAD51 paralogs, and each of these mutants exhibits embryonic lethality, although at different gestational stages. However, the phenotype of mice deficient in the fifth RAD51 paralog, XRCC3, has not been reported. Here we report that Xrcc3 knockout mice exhibit midgestational lethality, with mild phenotypes beginning at about E8.25 but severe developmental abnormalities evident by E9.0–9.5. The most obvious phenotypes are small size and a failure of the embryo to turn to a fetal position. A knockin mutation at a key ATPase residue in the Walker A box results in embryonic lethality at a similar stage. Death of knockout mice can be delayed a few days for some embryos by homozygous or heterozygous Trp53 mutation, in keeping with an important role for XRCC3 in promoting genome integrity. Given that XRCC3 is a unique member of one of two RAD51 paralog complexes with RAD51C, these results demonstrate that both RAD51 paralog complexes are required for mouse development.
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通讯作者：
Murray SA
影响因子：
3.8
作者：
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通讯作者：
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