Regulation of murine telomere length by Rtel:: An essential gene encoding a helicase-like protein
Regulation of murine telomere length by Rtel:: An essential gene encoding a helicase-like protein
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DOI：
10.1016/j.cell.2004.05.026
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发表时间：
2004-06-25
期刊：
影响因子：
64.5
通讯作者：
Lansdorp, PM
中科院分区：
文献类型：
--
作者：
Ding, H;Schertzer, M;Lansdorp, PM
对哺乳动物物种之间调节端粒长度多样性的基因知之甚少。一个候选基因位点先前被映射到远端小鼠Chr 2 q上的一个区域。在这一区域内，我们发现了一个与C.优雅的我们克隆了端粒长度调节基因（Rtel），并在小鼠中失活其表达。Rtel（-/-）小鼠在妊娠第10天至第11.5天死亡，神经系统、心脏、血管系统和胚外组织存在缺陷。Rtel（-/-）胚胎干细胞在体外分化时表现出端粒丢失，并显示出许多染色体断裂和融合。Rtel（+/-）小鼠与小家鼠的杂交表明，来自小家鼠亲本的Rtel是M. F1细胞中的spretus染色体。我们的结论是，Rtel是一个重要的基因，调节端粒长度，防止遗传不稳定性。
Little is known about the genes that regulate telomere length diversity between mammalian species. A candidate gene locus was previously mapped to a region on distal mouse Chr 2q. Within this region, we identified a gene similar to the dog-1 DNA helicase-like gene in C. elegans. We cloned this Regulator of telomere length (Rtel) gene and inactivated its expression in mice. Rtel(-/-) mice died between days 10 and 11.5 of gestation with defects in the nervous system, heart, vasculature, and extraembryonic tissues. Rtel(-/-) embryonic stem cells showed telomere loss and displayed many chromosome breaks and fusions upon differentiation in vitro. Crosses of Rtel(+/-) mice with Mus spretus showed that Rtel from the Mus musculus parent is required for telomere elongation of M. spretus chromosomes in F1 cells. We conclude that Rtel is an essential gene that regulates telomere length and prevents genetic instability.