Qi Ling, Strong Margaret A, Karim Baktiar O, Armanios Mary, Huso David L, Greider Carol W
Departments of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Cancer Res. 2003 Dec 1;63(23):8188-96.
To examine the role of ataxia-telangiectasia mutated (Atm) in telomere function, we generated Atm and telomerase null mice (Atm(-/-) mTR(-/-) iG6 mice). These mice exhibited increased germ cell death and chromosome fusions compared with either Atm(-/-) or mTR(-/-) iG6 mice. Furthermore, the Atm(-/-) mTR(--) iG6 mice had a delayed onset and reduced incidence of thymic lymphoma compared with Atm(-/-) mice. The tumors in the Atm(-/-) mTR(-/-) iG6 mice showed increased apoptosis and anaphase bridges. Finally, lymphomas from Atm(-/-) mTR(-/-) iG6 mice were derived from CD8 immature, single-positive T cells, whereas Atm(-/-) lymphomas were from CD4(+)CD8(+) double-positive T cells. We propose that Atm protects short telomeres and that Atm deficiency cooperates with short telomeres, leading to increased cell death, decreased tumorigenesis, and increased overall survival.
为了研究共济失调毛细血管扩张症突变基因（Atm）在端粒功能中的作用，我们培育了Atm和端粒酶缺失的小鼠（Atm(-/-) mTR(-/-) iG6小鼠）。与Atm(-/-) 或mTR(-/-) iG6小鼠相比，这些小鼠的生殖细胞死亡增加，染色体融合现象增多。此外，与Atm(-/-) 小鼠相比，Atm(-/-) mTR(-/-) iG6小鼠胸腺淋巴瘤的发病延迟且发病率降低。Atm(-/-) mTR(-/-) iG6小鼠的肿瘤显示出凋亡增加和后期桥接现象。最后，Atm(-/-) mTR(-/-) iG6小鼠的淋巴瘤来源于CD8未成熟单阳性T细胞，而Atm(-/-) 淋巴瘤则来源于CD4(+)CD8(+) 双阳性T细胞。我们认为Atm可保护短端粒，Atm缺陷与短端粒协同作用，导致细胞死亡增加、肿瘤发生减少以及总体生存期延长。
