Telomere-associated protein TIN2 is essential for early embryonic development through a telomerase-independent pathway.
TIN2 is a negative regulator of telomere elongation that interacts with telomeric DNA repeat binding factor 1 (TRF1) and affects telomere length by a telomerase-dependent mechanism. Here we show that inactivation of the mouse TRF1-interacting protein 2 (TIN2) gene results in early embryonic lethality. We further observed that the embryonic lethality of TIN2 mutant mice was not affected by inactivation of the telomerase reverse transcriptase gene, indicating that embryonic lethality is not the result of telomerase-dependent changes in telomere length or function. Our findings suggest that TIN2 has a role independent of telomere length regulation that is essential for embryonic development and cell viability.
Chiang
Y Jeffrey
YJ
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, 4B36, 9000 Rockville Pike, Bethesda, MD 20892, USA. chiangj@mail.nih.gov
Kim
Sahn-Ho
SH
Tessarollo
Lino
L
Campisi
Judith
J
Hodes
Richard J
RJ
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D015139:Blotting, Southern; D002470:Cell Survival; D004247:DNA / Q000737:chemistry; D018390:Gene Targeting; D005822:Genetic Vectors; D005838:Genotype; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D019098:Telomerase / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D013997:Time Factors
D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; C499083:Tinf2 protein, mouse; D004247:DNA; D019098:Telomerase