Blasco M A, Lee H W, Hande M P, Samper E, Lansdorp P M, DePinho R A, Greider C W
Cold Spring Harbor Laboratory, New York 11724, USA.
Cell. 1997 Oct 3;91(1):25-34. doi: 10.1016/s0092-8674(01)80006-4.
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.
为了研究端粒酶在正常生长和肿瘤生长中的作用，从小鼠种系中删除了端粒酶RNA成分（mTR）。mTR基因敲除小鼠缺乏可检测到的端粒酶活性，但在分析的六代中均存活。端粒酶缺陷细胞在培养中可永生化，可被病毒癌基因转化，并在转化后在裸鼠中产生肿瘤。端粒以每代mTR基因敲除小鼠4.8±2.4 kb的速度缩短。从第四代mTR基因敲除小鼠开始的细胞具有缺乏可检测到的端粒重复序列的染色体末端、非整倍体和染色体异常，包括端对端融合。这些结果表明，端粒酶对于维持端粒长度至关重要，但对于小鼠细胞系的建立、致癌转化或肿瘤形成并非必需。
