Inducing segmental aneuploid mosaicism in the mouse through targeted asymmetric sister chromatid event of recombination
Inducing segmental aneuploid mosaicism in the mouse through targeted asymmetric sister chromatid event of recombination
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DOI：
10.1534/genetics.108.092312
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发表时间：
2008-09-01
期刊：
影响因子：
3.3
通讯作者：
Herault, Yann
中科院分区：
文献类型：
--
作者：
Duchon, Arnaud;Besson, Vanessa;Herault, Yann
整个染色体或部分染色体的丢失或获得存在于各种病理状况中，例如癌症和非整倍性，并且是由细胞分裂期间的错误分离染色体或异常有丝分裂重组引起的。我们介绍了一种新的策略，用于确定节段性非整倍体嵌合的后果，称为靶向不对称姐妹染色质重组事件（TASCER）。我们利用Cre/loxP系统，广泛用于胚胎干细胞产生感兴趣的区域的缺失和重复，在G2期诱导重组。使用两个loxP位点的顺式配置，我们在体内产生的细胞窝藏微缺失和微重复的区域覆盖高达2.2 Mb的兴趣。在小鼠中使用这种方法提供了对人类21号染色体同源区域的节段性非整倍性对细胞存活的后果的洞察。此外，TASCER表明，Cre诱导的重组是更有效的DNA复制后，在体内，并提供了一个机会，通过遗传嵌合体，在小鼠中的拷贝数变异和节段性非整倍性的结果进行评估。
Loss or gain of whole chromosomes, or parts of chromosomes, is found in various pathological conditions, such as cancer and aneuploidy, and results from the missegregation chromosomes during cellular division or abnormal mitotic recombination. We introduce a novel strategy for determining the consequences of segmental aneuploid mosaicism, called targeted asymmetric sister chromatin event of recombitiation (TASCER). We took advantage of the Cre/loxP system, used extensively in embryonic stem cells for generating deletions and duplications of regions of interest, to induce recombination during the G2 phase. Using two loxP sites in a Cis configuration, we generated in vivo cells harboring microdeletions and microduplications for regions of interest covering up to 2.2 Mb. Using this approach in the mouse provides insight into the consequences of segmental aneuploidy for homologous regions of the human chromosome 21 on cell survival. Furthermore, TASCER shows that Cre-induced recombination is more efficient after DNA replication in vivo and provides an oppourtunity to evaluate, through genetic mosaics, the outcome of copy number variation and segmental aneuploidy in the mouse.