Liu Cuihua, Tanaka Kaoru, Katsube Takanori, Varès Guillaume, Maruyama Kouichi, Ninomiya Yasuharu, Fardous Zeenath, Sun Chao, Fujimori Akira, Moreno Stéphanie G, Nenoi Mitsuru, Wang Bing
National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Cell Signal Unit, Okinawa Institute of Science and Technology, Okinawa, Japan.
Dose Response. 2020 Aug 26;18(3):1559325820951332. doi: 10.1177/1559325820951332. eCollection 2020 Jul-Sep.
Application of green fluorescent protein (GFP) in a variety of biosystems as a unique bioindicator or biomarker has revolutionized biological research and made groundbreaking achievements, while increasing evidence has shown alterations in biological properties and physiological functions of the cells and animals overexpressing transgenic GFP. In this work, response to total body irradiation (TBI) was comparatively studied in GFP transgenic C57BL/6-Tg (CAG-EGFP) mice and C57BL/6 N wild type mice. It was demonstrated that GFP transgenic mice were more sensitive to radiation-induced bone marrow death, and no adaptive response could be induced. In the nucleated bone marrow cells of GFP transgenic mice exposed to a middle dose, there was a significant increase in both the percentage of cells expressing pro-apoptotic gene Bax and apoptotic cell death. While in wild type cells, lower expression of pro-apoptotic gene Bax and higher expression of anti-apoptotic gene Bcl-2, and significant lower induction of apoptosis were observed compared to GFP transgenic cells. Results suggest that presence of GFP could alter response to TBI at whole body, cellular and molecular levels in mice. These findings indicate that there could be a major influence on the interpretation of the results obtained in GFP transgenic mice.
绿色荧光蛋白（GFP）作为一种独特的生物指示剂或生物标志物在多种生物系统中的应用彻底改变了生物学研究并取得了突破性成就，与此同时，越来越多的证据表明，过表达转基因GFP的细胞和动物的生物学特性和生理功能发生了改变。在这项工作中，对绿色荧光蛋白转基因C57BL/6-Tg（CAG-EGFP）小鼠和C57BL/6 N野生型小鼠对全身照射（TBI）的反应进行了比较研究。结果表明，绿色荧光蛋白转基因小鼠对辐射诱导的骨髓死亡更敏感，且无法诱导适应性反应。在接受中等剂量照射的绿色荧光蛋白转基因小鼠的有核骨髓细胞中，表达促凋亡基因Bax的细胞百分比和凋亡细胞死亡均显著增加。而在野生型细胞中，与绿色荧光蛋白转基因细胞相比，促凋亡基因Bax的表达较低，抗凋亡基因Bcl-2的表达较高，且凋亡诱导显著较低。结果表明，绿色荧光蛋白的存在可在小鼠全身、细胞和分子水平上改变对全身照射的反应。这些发现表明，绿色荧光蛋白转基因小鼠所获结果的解读可能会受到重大影响。
