이한웅 (Albert Einstein College of Medicine, 현재 연세대학교) | 상위피인용논문 > 한빛사

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Albert Einstein College of Medicine, 현재 연세대학교

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Nature, 392, 569-574 (9 April 1998) | doi:10.1038/33345 Essential role of mouse telomerase in highly proliferative organs

Abstract

Han-Woong Lee^1,2,3, Maria A. Blasco^3,4,5, Geoffrey J. Gottlieb⁶, James W. Horner, II¹, Carol W. Greider^2,4 & Ronald A. DePinho¹

1.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
2.Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
3.Department of Immunology and Oncology, Centro Nacional de Biotecnologia/CSIC, Universidad Autonoma Madrid, Campus Cantoblanco, Madrid E-28049, Spain
4.Quest Diagnostics Incorporated, One Malcolm Avenue, Teterboro, New Jersey 07608, USA
5.These authors contributed equally to this work.
6.Present addresses: Department of Biochemistry and Molecular Biology, Ilchun Institute for Molecular Medicine, Seoul National University College of Medicine, Seoul 110-790, Korea (H.-W.L.) Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA (C.W.G.).

Correspondence to: Carol W. Greider^2,4 Correspondence and requests for materials should be addressed to R.A.D. or C.W.G.

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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