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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)