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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Recombination Between Inverted Loxp Sites Is Cytotoxic For Proliferating Cells And Provides A Simple Tool For Conditional Cell Ablation
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Recombination Between Inverted Loxp Sites Is Cytotoxic For Proliferating Cells And Provides A Simple Tool For Conditional Cell Ablation

机译：倒Loxp位点之间的重组对于增殖细胞具有细胞毒性，并为条件性细胞消融提供了简单的工具

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摘要

The loxP/Cre recombination system is a widely used tool for mouse functional genomics, in particular for in vivo conditional mutagen-esis. Depending on the relative orientation and position of loxP sites, Cre-mediated recombination can result in a variety of targeted genomic rearrangements. It was previously reported that loss of the loxP-carrying chromosome can occur when loxP sites are arranged in inverse orientation. By using a chromosome 2 carrying inverted loxP sites, we found that Cre-mediated recombination not only causes chromosomal loss but also triggers apoptosis. We show that targeted recombination between inverted loxP sites (TRIP) triggers cell death specifically in proliferating Cre-expressing cells, and we provide evidence that TRIP is an efficient tool to ablate proliferating cells within genetically defined cell populations. Furthermore, the procedure requires only a simple, one-step intercross but neither the use of toxins nor the additional step of prodrug injection. With the large repertoire of tissue-specific or inducible Cre-expressing transgenes available, TRIP-mediated cell ablation is valuable to investigate the function of a large variety of cell populations in the context of a whole organism, which includes mechanisms underlying organ development and tissue homeostasis.
机译：loxP / Cre重组系统是广泛用于小鼠功能基因组学的工具，尤其是用于体内条件诱变的工具。根据loxP位点的相对方向和位置，Cre介导的重组可导致多种目标基因组重排。以前有报道说，当loxP位点以反方向排列时，可能会丢失携带loxP的染色体。通过使用携带反向loxP位点的2号染色体，我们发现Cre介导的重组不仅导致染色体损失，而且还引发细胞凋亡。我们显示，反向loxP位点（TRIP）之间的靶向重组特别是在增生的表达Cre的细胞中触发细胞死亡，并且我们提供了TRIP是消融遗传定义的细胞群中增殖细胞的有效工具的证据。此外，该过程仅需要简单的一步交叉，而无需使用毒素，也不需要额外的前药注射步骤。有了可用的组织特异性或诱导性Cre表达转基因的丰富库，TRIP介导的细胞消融对于研究整个生物体中多种细胞群体的功能非常有价值，其中包括器官发育和组织的潜在机制稳态。

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