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. 2004 Aug;24(15):6631-4.
doi: 10.1128/MCB.24.15.6631-6634.2004.

Telomere-associated protein TIN2 is essential for early embryonic development through a telomerase-independent pathway

Y Jeffrey Chiang  1 , Sahn-Ho Kim, Lino Tessarollo, Judith Campisi, Richard J Hodes
Affiliations

Telomere-associated protein TIN2 is essential for early embryonic development through a telomerase-independent pathway

Y Jeffrey Chiang et al. Mol Cell Biol. 2004 Aug.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Generation of TIN2-deficient mice by gene targeting. (A) Gene targeting strategy and restriction map of the gene. The open boxes represent the exons of the TIN2 gene. A neomycin resistance gene was inserted into exon 1 5′ of the translation initiation codon ATG. (B) Southern blot analysis of mouse tail DNA. The 8.5- and 13-kb bands represent the germ line and targeted alleles, respectively. (C) PCR analysis for the TIN2 genotype. The 220- and 270-bp PCR products represent the wild-type and targeted alleles, respectively.
FIG. 2.
FIG. 2.
(A) PCR genotyping of 3.5-day-old TIN2 embryos. The 220- and 270-bp PCR products represent the wild-type and targeted alleles, respectively. (B) In vitro-cultured 3.5-day-old embryo in ES cell medium. Pictures in the upper panel represent individual TIN2+/− embryos after 5 days of culture. Pictures in the lower panel represent individual TIN2−/− embryos after 5 days of culture.
FIG. 2.
FIG. 2.
(A) PCR genotyping of 3.5-day-old TIN2 embryos. The 220- and 270-bp PCR products represent the wild-type and targeted alleles, respectively. (B) In vitro-cultured 3.5-day-old embryo in ES cell medium. Pictures in the upper panel represent individual TIN2+/− embryos after 5 days of culture. Pictures in the lower panel represent individual TIN2−/− embryos after 5 days of culture.
See this image and copyright information in PMC

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