Targeted deletion reveals an essential function for the telomere length regulator Trf1

Mol Cell Biol. 2003 Sep;23(18):6533-41. doi: 10.1128/mcb.23.18.6533-6541.2003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blastocyst / pathology
  • Cell Division
  • Cells, Cultured
  • Female
  • Fetal Death / genetics
  • Gene Targeting
  • Mice
  • Mice, Mutant Strains
  • Pregnancy
  • Sequence Deletion
  • Telomerase / deficiency
  • Telomerase / genetics
  • Telomere / physiology*
  • Telomeric Repeat Binding Protein 1 / genetics*
  • Telomeric Repeat Binding Protein 1 / metabolism*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Telomeric Repeat Binding Protein 1
  • Tumor Suppressor Protein p53
  • Telomerase