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Abstract
To examine the role of telomerase in normal and neoplastic 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 viral 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.