Haploinsufficiency of mTR results in defects in telomere elongation

Karen S. Hathcock, Michael T. Hemann, Kay Keyer Opperman, Margaret A. Strong, Carol W Greider, Richard J. Hodes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3591-3596
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number6
DOIs
StatePublished - Mar 19 2002

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Haploinsufficiency
Telomere
Telomerase
Knockout Mice

ASJC Scopus subject areas

  • Genetics
  • General

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Haploinsufficiency of mTR results in defects in telomere elongation. / Hathcock, Karen S.; Hemann, Michael T.; Opperman, Kay Keyer; Strong, Margaret A.; Greider, Carol W; Hodes, Richard J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 6, 19.03.2002, p. 3591-3596.

Research output: Contribution to journalArticle

Hathcock, Karen S. ; Hemann, Michael T. ; Opperman, Kay Keyer ; Strong, Margaret A. ; Greider, Carol W ; Hodes, Richard J. / Haploinsufficiency of mTR results in defects in telomere elongation. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 6. pp. 3591-3596.
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