Japanese researchers create first female clones from male mice using CRISPR
A new gene-editing tool called Y-CUT allows scientists to eliminate the Y chromosome, producing healthy, fertile female offspring from male cells.
Researchers in Japan have successfully created female clones from male mice, marking the first time this has been achieved in mammals. The breakthrough, detailed in a preprint on bioRxiv, demonstrates that male cells can be converted into female offspring, a feat that challenges long-standing biological assumptions about mammalian reproduction.
To achieve this, a team co-led by Takashi Ishiuchi of the University of Yamanashi and Shogo Matoba of the Riken BioResource Research Center developed a CRISPR-based tool named "Y-CUT." The technique targets and eliminates the Y chromosome by disrupting the specific mechanism that ensures its inheritance during cell division. The resulting female pups possess XO chromosomes—meaning they have only one X chromosome instead of the typical two—yet they remained healthy and fertile. The researchers further proved the viability of the method by creating female clones from cryopreserved male cells; these clones were subsequently able to mate with cloned males to produce healthy pups.
The biological barrier
In mammals, sex is typically determined by the presence of XX chromosomes for females and XY for males. While certain species, such as the Okinawa rubble goby, can naturally change sex, mammals have historically been unable to do so. Previous cloning attempts involving males only produced male offspring, which created a significant bottleneck for scientists attempting to preserve species. This research builds upon a broader history of mammalian cloning, including the cloning of black-footed ferrets, and follows 2023 breakthroughs by Katsuhiko Hayashi, who successfully created egg cells from male mice.
Implications for conservation
This development provides a critical new tool for wildlife conservation, particularly for "frozen zoos" that may only contain male samples of an endangered species. According to MIT Technology Review, the technique could potentially be used to rescue species where only male individuals remain. Beyond conservation, the ability to generate both sexes from a single edited line offers a more efficient pathway for producing genetically engineered animals. It also opens a new avenue for scientists to study the fundamental biological role of sex chromosomes.
Shifting scientific paradigms
The results suggest a fundamental shift in how reproductive biology is understood. "There’s a fixed concept in our scientific field that we need both females and males for reproduction," said Takashi Ishiuchi. "I think we could change this concept," he added, describing the process as being "like sci-fi." Monika Ward, a reproductive biologist at the University of Hawaii, noted that "no one has done this before."
As the findings move from preprint to peer review, the scientific community will be watching to see if the Y-CUT method can be scaled or applied to other mammalian species, and whether the XO chromosomal status presents any long-term health implications beyond the initial fertile generation.