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Severe growth defect in mouse cells lacking the telomerase RNA component

Nature Genetics volume 19, pages 203–206 (1998)Cite this article

Abstract

The ribonucleoprotein enzyme telomerase synthesizes telomeric DNA onto chromosome ends1. Telomere length is maintained, by the presence of telomerase activity, in the vast majority of primary tumours and stem cells2,3, suggesting that telomere maintenance is essential for cellular immortalization. Recently, the telomerase RNA component in human4 and mouse5 (TERC and Terc, respectively), a telomerase-associated protein TEP1/TLP1 (refs 6,7) and the human catalytic subunit protein TERT (Refs 8,9) have been identified. To examine the role of telomerase in telomere maintenance and cellular viability, we established Terc-deficient embryonic stem (ES) cells. It is known that telomerase activity is absent in cells from Terc-knockout mice10. Although the study showed that telomere shortening was observed in the Terc-deficient cells from first to six generation animals, whether telomerase-dependent telomere maintenance was essential for cellular viability remained to be elucidated. To address this issue, we examined Terc-deficient ES cells under long-term culture conditions. Accompanying the continual telomere shortening, the growth rate of Terc-deficient ES cells was gradually reduced after more than 300 divisions. An impaired growth rate was maintained to approximately 450 divisions, and then cell growth virtually stopped. These data clearly show that telomerase-dependent telomere maintenance is critical for the growth of mammalian cells.

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Figure 1: Generation of Terc-/- ES cells.
Figure 2: Growth of Terc-/- ES cells in long-term culture.
Figure 3: Telomere shortening in the Terc-/- cells.
Figure 4: FISH analysis of Terc-/- telomeres after long-term culture.

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Acknowledgements

We thank I. Saito for providing the recombinant Cre adenovirus, R. Narayanan for helpful discussions and comments and M. Shio for FISH analysis.

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Author notes

  1. Yoichi Shinkai

    Present address: Institute for Virus Research, Kyoto University, 53 Shogoin Kawara-cho, Sakyo-ku, Kyoto, 606-8397, Japan

Authors and Affiliations

  1. Nippon Roche Research Center, 200 Kajiwara, Kamakura, 247-8530, Japan

    Hiroyuki Niida, Hideo Satoh, Mieko Shiwa & Yoichi Shinkai

  2. Agene Research Institute, 200 Kajiwara, Kamakura, 247-8530, Japan

    Takehisa Matsumoto, Yoshiki Tokutake & Yasuhiro Furuichi

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Niida, H., Matsumoto, T., Satoh, H. et al. Severe growth defect in mouse cells lacking the telomerase RNA component . Nat Genet 19, 203–206 (1998). https://doi.org/10.1038/580

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