日本研究团队首次成功利用CRISPR技术开发的Y-CUT工具，从雄性小鼠胚胎中移除Y染色体，创造出具有遗传同一性的雌性克隆 [1]。这一突破挑战了哺乳动物繁殖需要两性参与的传统认知。山梨大学的Takashi Ishiuchi团队和理研生物资源研究中心的Shogo Matoba联合进行了该研究 [1]。
Y-CUT技术通过靶向Y染色体上的关键部分，使处理后的XY胚胎在代孕鼠中发育成健康、可育的雌性幼鼠，其染色体为XO [1]。研究人员利用冷冻保存的雄性细胞制造的雌性克隆与雄性克隆能够成功交配，产生健康的幼鼠 [1]。相比之下，该技术目前仍需依赖同物种或密切相关物种的空心卵细胞 [1]，且对于由XO染色体导致不育的哺乳动物可能作用有限 [1]。
研究结果已发表在bioRxiv预印本平台上，但尚未经过同行评审 [1]。科学家们认为这一方法在濒危物种保护中具有潜在应用价值，特别是考虑到全球有355种啮齿动物处于濒危或易危状态 [1]。
Researchers in Japan have successfully generated female clones of male mice for the first time, challenging long-held scientific assumptions about mammalian reproduction [1]. A team led by Takashi Ishiuchi at the University of Yamanashi and Shogo Matoba at the RIKEN Center for Biosource Research developed a CRISPR-based tool called Y-CUT that removes the Y chromosome from male mouse embryos [1]. When the processed XY embryos were transferred to surrogate mothers, they produced healthy, fertile female offspring with XO chromosomes that were genetically identical to the original males except for the absence of the Y chromosome [1].
The Y-CUT technology works by targeting critical regions of the Y chromosome that normally ensure female cells inherit the Y chromosome [1]. The breakthrough demonstrates that two biological sexes are not inherently necessary for mammalian reproduction [1]. Additionally, the researchers showed that female clones generated from frozen male cells can mate with male clones derived from the same source, producing healthy offspring [1]. However, the technique currently requires hollow egg cells from the same species or closely related species [1], and its effectiveness may be limited for mammals with XO chromosome-related infertility [1]. The findings, published on the bioRxiv preprint platform, have not yet undergone peer review [1]. With approximately 355 species of endangered or vulnerable rodents globally, this advancement holds potential applications for conservation efforts [1].
