靶向缺失揭示了端粒长度调节因子Trf1的重要功能。
Targeted deletion reveals an essential function for the telomere length regulator Trf1.
作者信息
Karlseder Jan, Kachatrian Leili, Takai Hiroyuki, Mercer Kim, Hingorani Sunil, Jacks Tyler, de Lange Titia
机构信息
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA.
出版信息
Mol Cell Biol. 2003 Sep;23(18):6533-41. doi: 10.1128/MCB.23.18.6533-6541.2003.
The human telomeric DNA binding factor TRF1 (hTRF1) and its interacting proteins TIN2, tankyrase 1 and 2, and PINX1 have been implicated in the regulation of telomerase-dependent telomere length maintenance. Here we show that targeted deletion of exon 1 of the mouse gene encoding Trf1 causes early (day 5 to 6 postcoitus) embryonic lethality. The absence of telomerase did not alter the Terf1(ex1Delta/ex1Delta) lethality, indicating that the phenotype was not due to inappropriate telomere elongation by telomerase. Terf1(ex1Delta/ex1Delta) blastocysts had a severe growth defect of the inner cell mass that was accompanied by apoptosis. However, no evidence was found for telomere uncapping causing this cell death; chromosome spreads of Terf1(ex1Delta/ex1Delta) blastocysts did not reveal chromosome end-to-end fusions, and p53 deficiency only briefly delayed Terf1(ex1Delta/ex1Delta) lethality. These data suggest that murine Trf1 has an essential function that is independent of telomere length regulation.
人类端粒DNA结合因子TRF1（hTRF1）及其相互作用蛋白TIN2、端锚聚合酶1和2以及PINX1参与了端粒酶依赖性端粒长度维持的调控。在此我们表明，靶向缺失小鼠Trf1基因的外显子1会导致早期（交配后第5至6天）胚胎致死。端粒酶的缺失并未改变Terf1（ex1Delta/ex1Delta）的致死性，这表明该表型并非由端粒酶不适当的端粒延长所致。Terf1（ex1Delta/ex1Delta）囊胚的内细胞团存在严重的生长缺陷，并伴有细胞凋亡。然而，未发现端粒解盖导致这种细胞死亡的证据；Terf1（ex1Delta/ex1Delta）囊胚的染色体铺展未显示染色体端对端融合，并且p53缺陷仅短暂延迟了Terf1（ex1Delta/ex1Delta）的致死性。这些数据表明，小鼠Trf1具有独立于端粒长度调控的重要功能。
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