Mouse Models for the Study of Telomerase

  1. Derek J. Chadwick Organizer and
  2. Gail Cardew Organizer
  1. María A. Blasco1,
  2. Han-Woong Lee2,
  3. Michael Rizen3,
  4. Douglas Hanahan3,
  5. Ron DePinho2 and
  6. Carol W. Greider4

Published Online: 28 SEP 2007

DOI: 10.1002/9780470515433.ch11

Ciba Foundation Symposium 211 - Telomeres and Telomerase

Ciba Foundation Symposium 211 - Telomeres and Telomerase

How to Cite

Blasco, M. A., Lee, H.-W., Rizen, M., Hanahan, D., DePinho, R. and Greider, C. W. (2007) Mouse Models for the Study of Telomerase, in Ciba Foundation Symposium 211 - Telomeres and Telomerase (eds D. J. Chadwick and G. Cardew), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470515433.ch11

Author Information

  1. 1

    Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus Cantoblanco, Madrid E-28049, Spain

  2. 2

    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461

  3. 3

    Department of Biochemistry and Biophysics, Hormone Research Institute, University of California, San Francisco, CA 94143-0534

  4. 4

    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724 USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471972785

Online ISBN: 9780470515433



  • mouse models;
  • telomerase rna expression;
  • squamous cell carcinoma;
  • immortalization;
  • telomerase activation


The ends of chromosomes, or telomeres, consist of short repeated sequences that are synthesized by a ribonucleoprotein–DNA polymerase called telomerase. The RNA component of telomerase is essential for enzyme activity. The maintenance of telomere length by telomerase has been proposed to be essential for cellular viability and to play an important role in cellular senescence and immortalization. We are interested in using the mouse as a model system for the study of telomerase. We studied telomerase activity and expression of the mouse telomerase RNA component (mTR) in two different transgenic mouse models of multistage tumorigenesis: models of islet cell carcinoma and squamous cell carcinoma. In both tumour models, telomerase activity was detected only in late-stage tumours, whereas the telomerase RNA was present at higher than normal levels in pre-neoplastic stages and increased further in late-stage tumours. However, the RNA levels did not parallel the amounts of telomerase activity detected, suggesting that regulation of telomerase activity does not correlate with the regulation of its RNA component. These results establish a direct correlation between progression to late-stage tumours and induction of telomerase activity, and suggest that the initial up-regulation of telomerase RNA is an early event. To address the role of telomerase during normal mouse development and tumour formation, we have constructed a knockout mouse for the mouse telomerase RNA, mTR/. These mice and the cell lines derived from them are telomerase deficient.