Targeted Deletion Reveals an Essential Function for the Telomere Length Regulator Trf1

摘要

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^ex1Δ/ex1Δ lethality, indicating that the phenotype was not due to inappropriate telomere elongation by telomerase. Terf1^ex1Δ/ex1Δ 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^ex1Δ/ex1Δ blastocysts did not reveal chromosome end-to-end fusions, and p53 deficiency only briefly delayed Terf1^ex1Δ/ex1Δ lethality. These data suggest that murine Trf1 has an essential function that is independent of telomere length regulation.