Targeted Deletion Reveals an Essential Function for the Telomere Length Regulator Trf1
Copyright policy )Targeted Deletion Reveals an Essential Function for the Telomere Length Regulator Trf1
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.
- Massachusetts Institute of Technology United States
- Rockefeller University United States
Telomere, Mice, Mutant Strains, Mice, Blastocyst, Pregnancy, Gene Targeting, Animals, Female, Telomeric Repeat Binding Protein 1, Tumor Suppressor Protein p53, Fetal Death, Telomerase, Cell Division, Cells, Cultured, Sequence Deletion
Telomere, Mice, Mutant Strains, Mice, Blastocyst, Pregnancy, Gene Targeting, Animals, Female, Telomeric Repeat Binding Protein 1, Tumor Suppressor Protein p53, Fetal Death, Telomerase, Cell Division, Cells, Cultured, Sequence Deletion
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