Telomere length regulation in mice is linked to a novel chromosome locus
Telomere length regulation in mice is linked to a novel chromosome locus
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DOI：
10.1073/pnas.95.15.8648
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发表时间：
1998-07-21
影响因子：
11.1
通讯作者：
Hodes, RJ
中科院分区：
文献类型：
--
作者：
Zhu, LX;Hathcock, KS;Hodes, RJ
人们对调节物种特异性端粒长度的机制知之甚少，特别是在哺乳动物物种中。因此，通过使用端粒长度不同的两种可育小鼠物种来研究端粒长度的遗传调控。小家鼠（端粒长度>25 kb）和小家鼠（端粒长度5-15 kb）用于产生F1杂交和相互回交，然后分析端粒长度的调节。该分析表明，在端粒长度不同的亲本种系细胞融合后，存在一种显性的反式作用机制，能够广泛延长体细胞中的端粒。使用 M. spretus 作为轮回亲本，进行了种间杂交的全基因组筛选，确定了 2 号远端染色体上的 5 厘摩区域，该区域主要控制观察到的物种特异性端粒长度调节。该基因座与编码已知端粒结合蛋白或端粒酶成分的候选基因不同。这些结果表明，定位到远端 2 号染色体的一个未鉴定基因调节小鼠的端粒长度。
Little is known about the mechanisms that regulate species-specific telomere length, particularly in mammalian species. The genetic regulation of telomere length was therefore investigated by using two inter-fertile species of mice, which differ in their telomere length. Mus musculus (telomere length >25 kb) and Mus spretus (telomere length 5-15 kb) were used to generate F1 crosses and reciprocal backcrosses, which were then analyzed for regulation of telomere length. This analysis indicated that a dominant and trans-acting mechanism exists capable of extensive elongation of telomeres in somatic cells after fusion of parental germline cells with discrepant telomere lengths. A genome wide screen of interspecific crosses, using M. spretus as the recurrent parent, identified a 5-centimorgan region on distal chromosome 2 that predominantly controls the observed species-specific telomere length regulation. This locus is distinct from candidate genes encoding known telomere-binding proteins or telomerase components. These results demonstrate that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse.