Remarkable Differences in Telomere Lengths among Cloned Cattle Derived from Different Cell Types1

Regarding cloned animals, interesting questions have been raised as to whether cloning restores cellular senescence undergone by their donor cells and how long cloned animals will be able to live. Focusing our attention on differences in telomere lengths depending on the tissue, we had produced 14 cloned cattle by using nuclei of donor cells derived from muscle, oviduct, mammary, and ear skin. Here, we show remarkable variation in telomere lengths among them using Southern blot analysis with telomere-specific probe. Telomere lengths in cloned cattle derived from muscle cells of an old bull were longer than those of a donor animal but were within the variation in normal calves. On the other hand, those derived from oviductal and mammary epithelial cells of an equally old cow were surprisingly shorter than any found in control cattle. The telomere lengths of cloned cattle derived from fibroblasts and oviductal epithelial cells of younger cattle showed the former and the latter results, respectively. In both cases, however, less telomere erosion or telomere extension from nuclear transfer to birth in most cloned cattle was observed in comparison with telomere erosion from fertilization to birth in control cattle. Embryonic cell-cloned cattle and their offspring calves were also shown to have telomeres longer than those in age-matched controls. These observations indicate that cloning does not necessarily restore the telomere clock but, rather, that nuclear transfer itself may commonly trigger an elongation of telomeres, probably more or less according to donor cell type. Remarkable variations among cloned cattle are suggested to be caused by variation in telomere