title: Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
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.
authors.affiliation: Cold Spring Harbor Laboratory, New York 11724, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Blasco
authors.forename: H W
authors.initials: HW
authors.lastname: Lee
authors.forename: M P
authors.initials: MP
authors.lastname: Hande
authors.forename: E
authors.initials: E
authors.lastname: Samper
authors.forename: P M
authors.initials: PM
authors.lastname: Lansdorp
authors.forename: R A
authors.initials: RA
authors.lastname: DePinho
authors.forename: C W
authors.initials: CW
authors.lastname: Greider
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000378:metabolism; D005347:Fibroblasts; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology*; D009928:Organ Specificity; D012313:RNA / Q000235:genetics / Q000502:physiology*; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D012313:RNA; D019098:Telomerase