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- Title
Telomere shortening in mTR<sup>-/-</sup> embryos is associated with failure to close the neural tube.
- Authors
Herrera, Eloísa; Samper, Enrique; Blasco, María A.
- Abstract
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.
- Publication
EMBO Journal, 1999, Vol 18, Issue 5, p1172
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/18.5.1172