First Author | Hathcock KS | Year | 2002 |
Journal | Proc Natl Acad Sci U S A | Volume | 99 |
Issue | 6 | Pages | 3591-6 |
PubMed ID | 11904421 | Mgi Jnum | J:81782 |
Mgi Id | MGI:2450002 | Doi | 10.1073/pnas.012549799 |
Citation | Hathcock KS, et al. (2002) Haploinsufficiency of mTR results in defects in telomere elongation. Proc Natl Acad Sci U S A 99(6):3591-6 |
abstractText | Telomeres are usually maintained about an equilibrium length, and the set point for this equilibrium differs between species and between strains of a given species. To examine the requirement for telomerase in mediating establishment of a new telomere length equilibrium, we generated interspecies crosses with telomerase mTR knockout mice. In crosses between C57BL/6J (B6) and either of two unrelated mouse species, CAST/Ei and SPRET/Ei, telomerase mediated establishment of a new telomere length equilibrium in wild-type mTR(+/+) mice. This new equilibrium was characterized by elongation of the short telomeres of CAST/Ei or SPRET/Ei origin. In contrast, mTR(-/-) offspring of interspecies crosses failed to elongate telomeres. Unexpectedly, haploinsufficiency was observed in mTR(+/-) heterozygous interspecies mice, which had an impaired ability to elongate short SPRET/Ei or CAST/Ei telomeres to the new equilibrium set point that was achieved in wild-type mTR(+/+) mice. These results demonstrate that elongation of telomeres to a new telomere set point requires telomerase and indicate that telomerase RNA may be limiting in vivo. |