Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice.
Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice.
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Rad52 的缺失可以部分挽救 Atm 缺陷小鼠的肿瘤发生和 T 细胞成熟。
DOI：
10.1038/sj.onc.1207604
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Barlow,Carrolee
中科院分区：
文献类型：
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作者：
Treuner,Kai;Helton,Rob;Barlow,Carrolee
共济失调毛细血管扩张症（AT）是一种常染色体隐性遗传疾病，由蛋白激酶ATM功能丧失引起。atm缺陷小鼠表现出与人类疾病一致的几种表型，包括癌症易感性、生长迟缓、细胞增殖缺陷和不育。AT患者发生淋巴瘤和白血病的风险增加数百倍，这些疾病通常具有高度侵袭性。通过基因缺失Rad 52蛋白减少同源重组，我们能够大大减少Atm−/−小鼠中T细胞淋巴瘤的发生，从而延长双突变小鼠的寿命。此外，我们能够部分挽救Atm−/−小鼠的T细胞发育。其他表型，包括生长缺陷，基因组不稳定性，不育和放射敏感性，没有挽救。我们的研究结果表明，过度重组是一个重要的贡献者在AT的肿瘤发生。
Ataxia Telangiectasia (AT) is an autosomal recessive disease caused by loss of function of the protein kinase ATM. Atm-deficient mice display several phenotypes consistent with the human disease, including predisposition to cancer, growth retardation, cell-proliferation defects and infertility. AT patients have a several hundred fold increased risk of developing lymphomas and leukemias, which are typically highly invasive. By reducing homologous recombination through genetic deletion of the Rad52 protein, we were able to decrease substantially the development of T-cell lymphomas in Atm−/− mice, resulting in an increased life span of the double mutant mice. Additionally, we were able to partially rescue the T-cell development of Atm−/− mice. Other phenotypes, including growth defects, genomic instability, infertility and radiosensitivity, were not rescued. Our results suggest that excessive recombination is an important contributor to tumorigenesis in AT.