Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans
Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans
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DOI：
10.1016/j.bbrc.2008.02.149
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发表时间：
2008-05-09
影响因子：
3.1
通讯作者：
Fushiki, Shinji
中科院分区：
文献类型：
--
作者：
Fujimori, Akira;Yaoi, Takeshi;Fushiki, Shinji
小头畸形是与宫内暴露的原子弹幸存者相关的畸形，并且可以通过胎儿暴露于电离辐射（IR）而在小鼠中诱发。然而，IR诱导的小头畸形的发病机制尚未完全清楚。我们的高覆盖率表达谱（HiCEP）分析表明，异常纺锤状小头畸形相关基因（ASPM）在辐射的人二倍体成纤维细胞下调。ASPM最近被报道为MCPH-5的致病基因，MCPH-5是人类最常见的先天性小头畸形类型。在这里，我们表明，Aspm基因的表达显着减少IR在各种人类和小鼠细胞。此外，ASPM被发现在辐射的胎鼠大脑中下调，特别是在脑室区。在辐照的神经球培养物中观察到类似的抑制。这是第一份报告表明，抑制Aspm的IR可能是最初的分子靶点，导致未来的小头畸形形成。(c)2008年爱思唯尔公司All rights reserved.
Microcephaly is a malformation associated with in utero exposed atomic bomb survivors and can be induced in mice by fetal exposure to ionizing radiation (IR). The pathogenesis of IR-induced microcephaly, however, has not been fully understood. Our analyses of high-coverage expression profiling (HiCEP) demonstrated that the abnormal spindle-like microcephaly associated gene (ASPM) was down-regulated in irradiated human diploid fibroblasts. ASPM was recently reported as the causative gene for MCPH-5, the most common type of congenital microcephaly in humans. Here, we show that the expression of the Aspm gene was significantly reduced by IR in various human and murine cells. Additionally, Aspm was found downregulated in the irradiated fetal mouse brain, particularly in the ventricular zones. A similar suppression was observed in the irradiated neurosphere cultures. This is the first report suggesting that the suppression of Aspm by IR could be the initial molecular target leading to the future microcephaly formation. (c) 2008 Elsevier Inc. All rights reserved.