Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA

TLDR

The study deleted the telomerase RNA component (mTR) from mouse germline to investigate telomerase’s role in normal and neoplastic growth. mTR‑/‑ mice lacked telomerase activity yet survived six generations; telomeres shortened rapidly, causing chromosome end loss, aneuploidy, and fusions, yet telomerase deficiency did not prevent cell immortalization, oncogenic transformation, or tumor formation in nude mice.

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.