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Published online on January 16, 2001, 10.1073/pnas.031559298
PNAS | January 30, 2001 | vol. 98 | no. 3 | 1077-1082


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Developmental Biology
 Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle

Dean H. Betts*, Vilceu Bordignondagger , Jonathan R. HillDagger , Quinton Winger§, Mark E. Westhusin§, Lawrence C. Smithdagger , and W. Allan King*,

* Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1; dagger  Centre de Recherche en Reproduction Animale, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada J2S 7C6; Dagger  Section of Theriogenology, Department of Clinical Sciences, Veterinary Research Tower VRT 7-002, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401; and § Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466

Communicated by James E. Womack, Texas A&M University, College Station, TX, November 27, 2000 (received for review August 1, 2000)

Nuclear reprogramming requires the removal of epigenetic modifications imposed on the chromatin during cellular differentiation and division. The mammalian oocyte can reverse these alterations to a state of totipotency, allowing the production of viable cloned offspring from somatic cell nuclei. To determine whether nuclear reprogramming is complete in cloned animals, we assessed the telomerase activity and telomere length status in cloned embryos, fetuses, and newborn offspring derived from somatic cell nuclear transfer. In this report, we show that telomerase activity was significantly (P < 0.05) diminished in bovine fibroblast donor cells compared with embryonic stem-like cells, and surprisingly was 16-fold higher in fetal fibroblasts compared with adult fibroblasts (P < 0.05). Cell passaging and culture periods under serum starvation conditions significantly decreased telomerase activity by approximately 30-50% compared with nontreated early passage cells (P < 0.05). Telomere shortening was observed during in vitro culture of bovine fetal fibroblasts and in very late passages of embryonic stem-like cells. Reprogramming of telomerase activity was apparent by the blastocyst stage of postcloning embryonic development, and telomere lengths were longer (15-23 kb) in cloned fetuses and offspring than the relatively short mean terminal restriction fragment lengths (14-18 kb) observed in adult donor cells. Overall, telomere lengths of cloned fetuses and newborn calves (approx 20 kb) were not significantly different from those of age-matched control animals (P > 0.05). These results demonstrate that cloned embryos inherit genomic modifications acquired during the donor nuclei's in vivo and in vitro period but are subsequently reversed during development of the cloned animal.

To whom reprint requests should be addressed. E-mail: waking{at}uoguelph.ca.


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