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Essential role of mouse telomerase in highly proliferative organs

Nature volume 392, pages 569–574 (1998)Cite this article

Abstract

We have investigated the role of the enzyme telomerase in highly proliferative organs in successive generations of mice lacking telomerase RNA. Late-generation animals exhibited defective spermatogenesis, with increased programmed cell death (apoptosis) and decreased proliferation in the testis. The proliferative capacity of haematopoietic cells in the bone marrow and spleen was also compromised. These progressively adverse effects coincided with substantial erosion of telomeres (the termini of eukaryotic chromosomes) and fusion and loss of chromosomes. These findings indicate an essential role for telomerase, and hence telomeres, in the maintenance of genomic integrity and in the long-term viability of high-renewal organ systems.

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Figure 1: Effects of lack of telomerase on the mouse reproductive system.
Figure 2: Proliferation and apoptosis in the male germ-cell compartment.
Figure 3: Effects of the lack of telomerase on haematopoietic cells.
Figure 4: Response of lymphocytes to lack of telomerase.

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Acknowledgements

We thank L. Cannizzaro, M. Zohouri, D. Gebhard, R. Mazzaccaro, B. Furman, K.E.Cedeno-Baier, L. Husted, A. Silverman, N. Squillante, H. Hou and J. Lauridsen for advice and assistance; N. Schreiber-Agus, R. Greenberg, L. Chin, J. Pollard, E. R. Stanley and R. Kucherlapati for critical reading of the manuscript and advice; and E. Herrera and J. M. Caballero for sharing the dermatitis data collected in the National Center of Biotechnology (Madrid) before publication. Work in the lab of R.A.D. was supported by the NIH, AHA Grant-in-Aid and a Liver Center Initiative. R.A.D. is a recipient of the Irma T. Hirschl Career Scientist Award. R.A.D. and C.W.G. are also supported by Cancer Core grants. Work in the lab of C.W.G. was supported by the NIH and by Geron Corporaiton. M.A.B. was supported by the Leukemia Society of America, a grant from the Ministry of Education of Spain, and the Department of Immunology and Oncology (founded by the Spanish research Council and Pharmacia-Upjohn). H.W.L. was supported by an NIH postdoctoral training grant.

Author information

Author notes

  1. Han-Woong Lee

    Present address: Department of Biochemistry and Molecular Biology, Ilchun Institute for Molecular Medicine, Seoul National University College of Medicine, Seoul, 110-790, Korea

  2. Carol W. Greider

    Present address: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

  3. Han-Woong Lee and Maria A. Blasco: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 10461, New York , USA

    Han-Woong Lee, James W. Horner II & Ronald A. DePinho

  2. Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, 11724, New York, USA

    Maria A. Blasco & Carol W. Greider

  3. Department of Immunology and Oncology Centro Nacional de Biotecnologia/CSIC, Universidad Autonoma Madrid, Campus Cantoblanco, Madrid, E-28049, Spain

    Maria A. Blasco

  4. Quest Diagnostics Incorporated, One Malcolm Avenue, Teterboro, 07608, New Jersey, USA

    Geoffrey J. Gottlieb

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Lee, HW., Blasco, M., Gottlieb, G. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 (1998). https://doi.org/10.1038/33345

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