Telomere shortening and tumor formation by mouse cells lacking telomerase RNA

María A. Blasco, Han Woong Lee, M. Prakash Hande, Enrique Samper, Peter M. Lansdorp, Ronald A. DePinho, Carol W. Greider

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1685 Citations (Scopus)

Abstract

To examine the role of telomerase in normal and neo-plastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. mTR (-/- ) mice lacked detectable telomerase activity yet were viable for the six generations analyzed. Telomerase-deficient cells could be immortalized in culture, transformed by vital oncogenes, and generated tumors in nude mice following transformation. Telomeres were shown to shorten at a rate of 4.8 ± 2.4 kb per mTR(-/-) generation. Cells from the fourth mTR(-/-) generation onward possessed chromosome ends lacking detectable telomere repeats, aneuploidy, and chromosomal abnormalities, including end-to-end fusions. These results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice.

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalCell
Volume91
Issue number1
DOIs
Publication statusPublished - 1997 Oct 3

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Blasco, M. A., Lee, H. W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997). Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell, 91(1), 25-34. https://doi.org/10.1016/S0092-8674(01)80006-4