, Volume 113, Issue 2, pp 62–68 | Cite as

Genomic instability in both wild-type and telomerase null MEFs

  • Ling-Yang Hao
  • Carol W. Greider
Research Article


To examine chromosome instability in the absence of telomerase, we established mouse embryonic fibroblast (MEF) lines from late generation mTR−/− and wild-type animals and examined metaphases using telomere fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY). In early passages, mTR−/− G6 cell lines showed more chromosome ends with no telomere signal, more chromosome end-to-end fusions and greater radiosensitivity than wild-type lines. At later passages, however, the rate of genomic instability in the wild-type MEFs increased to a level similar or higher than seen in the mTR−/− G6 cell lines. This high degree of instability in wild-type MEF lines suggests that post-crisis MEFs should not be considered genetically defined cell lines. Surprisingly, the increased radiosensitivity seen in early passage mTR−/− G6 cultures was lost after crisis. Both post-crisis mTR−/− G6 MEFs and wild-type MEFs showed loss of p53 and γ-H2AX phosphorylation in response to irradiation, indicating a loss of DNA damage checkpoints.


Telomere Length Mouse Embryonic Fibroblast Telomere Repeat Mouse Embryonic Fibroblast Cell H2AX Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Drs. Michael Hemann, Forrest Spencer and members of the Greider laboratory for critical reading of the manuscript, Margaret Strong for technical support and Dr. Steve Elledge for providing the Chk2 antibody. This work was supported by NIH grant CA16519 to C.W.G.

Supplementary material

412_2004_0291.pdf (529 kb)
(PDF 397 KB)


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Graduate Program in Human Genetics, Department of Molecular Biology and GeneticsJohns Hopkins University School of MedicineBaltimoreUSA

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