Short Telomeres Result in Organismal Hypersensitivity to Ionizing Radiation in Mammals

doi:10.1084/jem.192.11.1625

Published online 4 December 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1625/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1625-1636

Original Article

Short Telomeres Result in Organismal Hypersensitivity to Ionizing Radiation in Mammals

Fermín A. Goytisolo^a, Enrique Samper^a, Juan Martín-Caballero^a, Paul Finnon^b, Eloísa Herrera^a, Juana M. Flores^c, Simon D. Bouffler^b, and María A. Blasco^a
^a Department of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Campus Cantoblanco, E-28049 Madrid, Spain
^b Radiation Effects Department, National Radiological Protection Board, Oxfordshire OX11 ORQ, United Kingdom
^c Department of Animal Pathology II, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain

Correspondence to: María A. Blasco, Dept. of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Campus Cantoblanco, E-28049 Madrid, Spain. Tel:34-915854846 Fax:34-913720493 E-mail:mblasco{at}cnb.uam.es.

Here we show a correlation between telomere length and organismalsensitivity to ionizing radiation (IR) in mammals. In particular,fifth generation (G5) mouse telomerase RNA (mTR)^-/- mice, withtelomeres 40% shorter than in wild-type mice, are hypersensitiveto cumulative doses of gamma rays. 60% of the irradiated G5mTR^-/- mice die of acute radiation toxicity in the gastrointestinaltract, lymphoid organs, and kidney. The affected G5 mTR^-/- miceshow higher chromosomal damage and greater apoptosis than similarlyirradiated wild-type controls. Furthermore, we show that G5mTR^-/- mice show normal frequencies of sister chromatid exchangeand normal V(D)J recombination, suggesting that short telomeresdo not significantly affect the efficiency of DNA double strandbreak repair in mammals. The IR-sensitive phenotype of G5 mTR^-/-mice suggests that telomere function is one of the determinantsof radiation sensitivity of whole animals.

Key Words: telomerase, radiosensitivity, DNA DSB repair, cancer, radiotherapy

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