title: Haploinsufficiency of mTR results in defects in telomere elongation.
abstract: 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.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, and National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Hathcock
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
authors.forename: Kay Keyer
authors.initials: KK
authors.lastname: Opperman
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Strong
authors.forename: Carol W
authors.initials: CW
authors.lastname: Greider
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hodes
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D013045:Species Specificity; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase