SENS Research Foundation, 110 Pioneer Way, Suite J, Mountain View, CA, 94041, USA.
National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan.
Sci Rep. 2020 Nov 5;10(1):19080. doi: 10.1038/s41598-020-75867-z.
Exposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish healthspan and accelerate aging. We have developed a Drosophila melanogaster model to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using 156 strains from the Drosophila Genetic Reference Panel) to search for natural genetic variants that regulate radiation-induced gut permeability in adult D. melanogaster. From this screen, we identified an RNA binding protein, Musashi (msi), as one of the possible genes associated with changes in intestinal permeability upon radiation. The overexpression of msi promoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced intestinal permeability. In summary, we have established D. melanogaster as an expedient model system to study the effects of radiation-induced damage to the intestine in adults and have identified msi as a potential therapeutic target.
暴露于环境因素或治疗方法（如放射疗法）引起的遗传毒性应激会缩短健康寿命并加速衰老。我们开发了一种黑腹果蝇模型来研究辐射诱导损伤和修复的分子效应。利用定量肠通透性测定法，我们进行了一项无偏的全基因组关联研究（使用来自黑腹果蝇遗传参考面板的 156 个品系），以寻找调节成年黑腹果蝇辐射诱导肠通透性的天然遗传变异。从该筛选中，我们鉴定出一种 RNA 结合蛋白 Musashi（msi），作为与辐射后肠通透性变化相关的可能基因之一。msi 的过表达促进了肠干细胞的增殖，从而增加了照射后的存活率并挽救了辐射诱导的肠通透性。总之，我们已经建立了黑腹果蝇作为研究成年肠道辐射损伤效应的便捷模型系统，并鉴定出 msi 作为一个潜在的治疗靶点。
