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PMID: 11520856 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/- mice with short telomeres.

EMBO reports ·Vol. 2 ·No. 9 ·2001-09-00 ·Pages 800-7

Samper E, Flores JM, Blasco MA

Abstract

Reconstitution of telomerase activity is proposed as a potential gene therapy to prevent, or rescue, age-related diseases produced by critical telomere shortening. However, it is not known whether or not short telomeres are irreversibly damaged. We addressed this by re-introducing telomerase in late generation telomerase-deficient mice, Terc-/-, which have short telomeres and show severe proliferative defects. For this, we have crossed these mice with Terc+/- mice and analyzed telomere length, chromosomal instability and premature aging of the progeny. The Terc-/- progeny had one set of chromosomes with normal telomeres, whereas the other set remained with critically short telomeres; these mice presented chromosomal instability and premature aging. In contrast, Terc+/- progeny showed all chromosomes with detectable telomeres, and did not show chromosomal instability or premature aging. These results prove that critically short telomeres can be rescued by telomerase, and become fully functional, thus rescuing premature aging. This has important implications for the future design of telomerase-based gene therapy of age-related diseases.

MeSH Terms
Aging Animals Bone Marrow/pathology Bone Marrow Cells Chromosome Aberrations Chromosomes/metabolism,physiology Crosses, Genetic Genotype In Situ Hybridization, Fluorescence Intestine, Small/pathology Male Mice Mice, Transgenic Phenotype Telomerase/genetics,metabolism Telomere/metabolism,physiology Testis/pathology Y Chromosome/metabolism
Chemicals
Telomerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Samper E
Department of Immunology and Oncology, National Centre of Biotechnology, E-28049 Madrid, Spain.
Flores J M
Blasco M A
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1093/embo-reports/kve174
Published
2001-09-00
Epub
2001-00-23
Pages
800-7
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1084029
Subset
IM
External Links
PubMed source DOI: 10.1093/embo-reports/kve174 PMC Full Text View journal details
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