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Disease states associated with telomerase deficiency appear earlier in mice with short telomeres
Open accessAbstract
Mice deficient for the mouse telomerase RNA (mTR-/-) and lacking telomerase activity can only be bred for approximately six generations due to decreased male and female fertility and to an increased embryonic lethality associated with a neural tube closure defect. Although late generation mTR-/- mice show defects in the hematopoietic system, they are viable to adulthood, only showing a decrease in viability in old age. To assess the contribution of genetic background to the effect of telomerase deficiency on viability, we generated mTR-/- mutants on a C57BL6 background, which showed shorter telomeres than the original mixed genetic background C57BL6/129Sv. Interestingly, these mice could be bred for only four generations and the survival of late generation mTR-/- mice decreased dramatically with age as compared with their wild-type counterparts. Fifty percent of the generation 4 mice die at only 5 months of age. This decreased viability with age in the late generation mice is coincident with telomere shortening, sterility, splenic atrophy, reduced proliferative capacity of B and T cells, abnormal hematology and atrophy of the small intestine. These results indicate that telomere shortening in mTR-/- mice leads to progressive loss of organismal viability.
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“However, the cyclin-dependent kinase inhibitor p21 has been shown to participate in the p53-dependent telomere checkpoint response in both human fibroblasts and in TERCÀ/À mice (66,76).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [76]
In the citing paper
“Although it was initially clear that high-turnover tissues are particularly sensitive to telomere length85,101,112”
From The telomere syndromes (2012) · cites this paper as [112]
In the citing paper
“In particular, mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and a premature development of age-related pathologies from the second or third generation [8, 18–20, 51, 70, 72, 101, 103]”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [51]
In the citing paper
“the generation and characterization of the telomerase knockout mouse model has been instrumental in demonstrating that short telomeres result in multiple organismal defects caused by defective tissue regeneration 57, 58, 59”
From The common biology of cancer and ageing (2007) · cites this paper as [59]
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Self-citation
Metadata
- Authors
- Herrera, E., Samper, E., Martín‐Caballero, J., Flores, J. M., Lee, H., & Blasco, M. A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Universidad Complutense de Madrid (ES)
- Samsung Biomedical Research Institute (KR)
- Corresponding author
- Blasco, María A.
- Venue
- The EMBO Journal
- Published
- 1999-06-01
- Volume
- 18
- Issue
- 11
- Pages
- 2950-2960
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1171377
- OpenAlex
- W2153094950
- Semantic Scholar
- 2fedd51810926e4acbca1ade7ab5eecd55623631
- Cited by
- 471
- References
- 45
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 15 · 2017: 15 · 2016: 14 · 2015: 9 · 2014: 18 · 2013: 20 · 2012: 20
- FWCI
- 14.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Molecular Biology Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- telomerase deficiency, telomere shortening, genetic background effects, age-related mortality, fertility, embryonic lethality, neural tube defects, hematopoietic defects, splenic atrophy, hematological abnormalities
- MeSH terms
- Aging, Animals, Atrophy, Body Weight, Cells, Cultured, Crosses, Genetic, Female, Genes, Lethal, Hematopoietic System, Infertility, Intestine, Small, Leukocyte Count, Longevity, Lymphocytes, Male, Mice, Inbred C57BL, Spleen, Testis, Time Factors, Telomere, Mice, Knockout, Telomerase, Mice
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