| First Author | Herrera E | Year | 1999 |
| Journal | EMBO J | Volume | 18 |
| Issue | 5 | Pages | 1172-81 |
| PubMed ID | 10064584 | Mgi Jnum | J:53600 |
| Mgi Id | MGI:1332976 | Doi | 10.1093/emboj/18.5.1172 |
| Citation | Herrera E, et al. (1999) Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. EMBO J 18(5):1172-81 |
| abstractText | 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. |
