Maintaining genome integrity in the germline is essential for survival and propagation of a species. In both mouse and human, germ cells originate during fetal development and are hypersensitive to both endogenous and exogenous DNA damaging agents. Currently, mechanistic understanding of how primordial germ cells respond to DNA damage is limited in part by the tools available to study these cells. We developed a mouse transgenic reporter strain expressing a 53BP1‐mCherry fusion protein under the control of the Oct4ΔPE embryonic germ cell‐specific promoter. This reporter binds sites of DNA double strand breaks (DSBs) on chromatin, forming foci. Using ionizing radiation as a DNA DSB‐inducing agent, we show that the transgenic reporter expresses specifically in the embryonic germ cells of both sexes and forms DNA damage induced foci in both a dose‐ and time‐dependent manner. The dynamic time‐sensitive and dose‐sensitive DNA damage detection ability of this transgenic reporter, in combination with its specific expression in embryonic germ cells, makes it a versatile and valuable tool for increasing our understanding of DNA damage responses in these unique cells.

中文翻译：

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一种用于体内检测胚胎生殖细胞 DNA 损伤的报告小鼠。

保持种系中基因组的完整性对于物种的生存和繁殖至关重要。在小鼠和人类中，生殖细胞起源于胎儿发育过程，并且对内源性和外源性 DNA 损伤剂都非常敏感。目前，对原始生殖细胞如何应对 DNA 损伤的机制理解部分受到可用于研究这些细胞的工具的限制。我们开发了一种在 Oct4ΔPE 胚胎生殖细胞特异性启动子控制下表达 53BP1-mCherry 融合蛋白的小鼠转基因报告菌株。该报告基因结合染色质上的 DNA 双链断裂 (DSB) 位点，形成病灶。使用电离辐射作为 DNA DSB 诱导剂，我们表明转基因报告基因在两性的胚胎生殖细胞中特异性表达，并以剂量​​和时间依赖性方式形成 DNA 损伤诱导的病灶。这种转基因报告基因的动态时间敏感性和剂量敏感性 DNA 损伤检测能力，结合其在胚胎生殖细胞中的特异性表达，使其成为一种通用且有价值的工具，可用于增加我们对这些独特细胞中 DNA 损伤反应的理解。