Telomere shortening and tumor formation by mouse cells lacking telomerase RNA

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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.

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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

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