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首页> 外文期刊>Radiation Research: Official Organ of the Radiation Research Society >Mrad9 and atm haploinsufficiency enhance spontaneous and X-ray-induced cataractogenesis in mice
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Mrad9 and atm haploinsufficiency enhance spontaneous and X-ray-induced cataractogenesis in mice

机译：Mrad9和atm单倍剂量不足会增强小鼠自发性和X射线诱发的白内障发生

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摘要

Rad9 and Atm regulate multiple cellular responses to DNA damage, including cell cycle checkpoints, DNA repair and apoptosis. However, the impact of dual heterozygosity for Atm and Rad9 is unknown. Using 50 cGy of X rays as an environmental insult and cataractogenesis as an end point, this study examined the effect of heterozygosity for one or both genes in mice. Posterior subcapsular cataracts, characteristic of radiation exposure, developed earlier in X-irradiated double heterozygotes than in single heterozygotes, which were more prone to cataractogenesis than wild-type controls. Cataract onset time and progression in single or double heterozygotes were accelerated even in unirradiated eyes. These findings indicate that the cataractogenic effect of combined heterozygosity is greater than for each gene alone and are the first to demonstrate the impact of multiple haploinsufficiency on radiation effects in an intact mammal. These observations may help explain observed interindividual differential radiosensitivity in human populations and have important implications for those undergoing radiotherapy or exposed to elevated levels of cosmic. radiation, such as the astronaut corps. These findings demonstrate that Mrad9 and Atm are important determinants of lens opacification and, given the roles of Atm and Rad9 in maintaining genomic stability, are consistent with a genotoxic basis for radiation cataractogenesis.
机译：Rad9和Atm调节多种细胞对DNA损伤的反应，包括细胞周期检查点，DNA修复和凋亡。但是，双重杂合性对Atm和Rad9的影响尚不清楚。使用50 cGy的X射线作为环境侵害并以白内障发生为终点，本研究检查了小鼠中一个或两个基因的杂合性影响。 X射线照射的双杂合子比单杂合子更早地发展出具有辐射暴露特性的后囊状白内障，后者比野生型对照更容易发生白内障。即使在未经辐照的眼睛中，白内障的发作时间和单或双杂合子的进展也被加速。这些发现表明，混合杂合性的致白内障作用大于单独的每个基因，并且是第一个证明完整单倍体功能不足对完整哺乳动物的放射作用的影响。这些观察结果可能有助于解释在人群中观察到的个体间不同的放射敏感性，并对正在接受放射治疗或暴露于高水平宇宙的人们具有重要意义。辐射，例如宇航员。这些发现表明，Mrad9和Atm是晶状体混浊的重要决定因素，考虑到Atm和Rad9在维持基因组稳定性中的作用，与放射白内障的遗传毒性基础一致。

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