title: Targeted deletion reveals an essential function for the telomere length regulator Trf1.
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.
authors.affiliation: Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
authors.forename: Leili
authors.initials: L
authors.lastname: Kachatrian
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takai
authors.forename: Kim
authors.initials: K
authors.lastname: Mercer
authors.forename: Sunil
authors.initials: S
authors.lastname: Hingorani
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.forename: Titia
authors.initials: T
authors.lastname: de Lange
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D005313:Fetal Death / Q000235:genetics; D018390:Gene Targeting; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy; D017384:Sequence Deletion; D019098:Telomerase / Q000172:deficiency / Q000235:genetics; D016615:Telomere / Q000502:physiology*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D035321:Telomeric Repeat Binding Protein 1; D016159:Tumor Suppressor Protein p53; D019098:Telomerase