TELOMERE SHORTENING AND TUMOR-FORMATION BY MOUSE CELLS LACKING TELOMERASE RNA

To examine the role of telomerase in normal and neoplastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. m TR(-/-) mice lacked detectable telomerase activity yet were viable for the six generations analyzed. Telomerase-deficient cells could be imm ortalized in culture, transformed by viral oncogenes, and generated tu mors in nude mice following transformation. Telomeres were shown to sh orten at a rate of 4.8 +/- 2.4 kb per mTR(-/-) generation. Cells from the fourth mTR(-/-) generation onward possessed chromosome ends lackin g detectable telomere repeats, aneuploidy, and chromosomal abnormaliti es, including end-to-end fusions. These results indicate that telomera se is essential for telomere length maintenance but is not required fo r establishment of cell lines, oncogenic transformation, or tumor form ation in mice.