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EMBO J. 1999 Mar 1;18(5):1172-81.

Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube.

Author information

  • 1Department of Immunology and Oncology, Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, Madrid E-28049, Spain.

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.

PMID:
10064584
[PubMed - indexed for MEDLINE]
PMCID:
PMC1171208
Free PMC Article
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