Telomere shortening in mTR−/− embryos is associated with failure to close the neural tube
Open accessAbstract
Mice genetically deficient for the telomerase RNA (mTR) can be propagated for only a limited number of generations. In particular, mTR-/- mice of a mixed C57BL6/129Sv genetic background are infertile at the sixth generation and show serious hematopoietic defects. Here, we show that a percentage of mTR-/- embryos do not develop normally and fail to close the neural tube, preferentially at the forebrain and midbrain. The penetrance of this defect increases with the generation number, with 30% of the mTR-/- embryos from the fifth generation showing the phenotype. Moreover, mTR-/- kindreds in a pure C57BL6 background are only viable up to the fourth generation and also show defects in the closing of the neural tube. Cells derived from mTR-/- embryos that fail to close the neural tube have significantly shorter telomeres and decreased viability than their mTR-/- littermates with a closed neural tube, suggesting that the neural tube defect is a consequence of the loss of telomere function. The fact that the main defect detected in mTR-/- embryos is in the closing of the neural tube, suggests that this developmental process is among the most sensitive to telomere loss and chromosomal instability.
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Mice lacking mTR survived for four to six generations with few detectable phenotypic changes, depending on their genetic backgrounds.
“Depending on their genetic backgrounds, these mice survived for four to six generations with few detectable phenotypic changes (13, 14);”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [14]
In some genetic backgrounds, an increased incidence of neural tube defects limited viability of mTR-deficient mice after only four generations.
“In some genetic backgrounds, an increased incidence of neural tube defects limited viability after only four generations (14).”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [14]
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- Authors
- Herrera, E., Samper, E., & Blasco, M. A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Blasco, María A.
- Venue
- The EMBO Journal
- Published
- 1999-03-01
- Volume
- 18
- Issue
- 5
- Pages
- 1172-1181
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1171208
- OpenAlex
- W2019317570
- Cited by
- 147
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 8 · 2012: 4
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Spinal Dysraphism and Malformations
- Keywords
- telomere shortening, telomerase RNA, neural tube closure, neural tube defects, forebrain, midbrain, chromosomal instability, embryonic lethality, telomere loss
- MeSH terms
- Animals, Cell Survival, Central Nervous System, Embryonic and Fetal Development, Litter Size, Neural Tube Defects, Phenotype, RNA, Messenger, Telomere, In Situ Hybridization, In Situ Hybridization, Fluorescence, Mice, Knockout, Gene Expression Regulation, Developmental, Telomerase, In Situ Nick-End Labeling, Mice
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