Japanese researchers create female clones from male mice using CRISPR

Researchers in Japan have used a CRISPR-based tool to eliminate the Y chromosome from male mouse embryos and adult cells, creating female clones of male mice for the first time. The technique, called Y-CUT, targets a region of the Y chromosome essential for its inheritance during cell division. When applied to early-stage XY embryos, the treatment produced female pups with a single X chromosome (XO) that grew up healthy and fertile.

The team, led by Takashi Ishiuchi of the University of Yamanashi and Shogo Matoba of the Riken BioResource Research Center, also applied Y-CUT to cloned cells derived from adult male mice. After transferring the edited cells into surrogate mothers, they obtained female clones genetically identical to the male donor except for the missing Y chromosome. In additional experiments, the researchers created female clones from cryopreserved male cells, and the resulting male and female clones mated to produce healthy offspring.

The findings were published as a preprint on bioRxiv in August 2026 and have not yet undergone peer review. Reproductive biologist Monika Ward of the University of Hawaii, who was not involved in the work, said no one has achieved this deliberate sex reversal in mammals before. Ben Novak of the conservation organization Revive & Restore called the development exciting and predicted broad applications for endangered species recovery.

The work was inspired by fish such as the Okinawa rubble goby, which can change sex when population dynamics demand it. In conservation cloning, a major limitation has been that cloning a male yields only males, which does not help if a species' last survivors are all male. Y-CUT could allow scientists to generate females from stored male tissue samples held in "frozen zoos," potentially restoring breeding pairs.

The approach has constraints. It requires enucleated egg cells from females of the same or a closely related species, so it cannot help species where only females survive. Also, while XO female mice are fertile, many other mammals with a single X chromosome experience infertility, limiting the technique's immediate utility across the 355 endangered or vulnerable rodent species and other mammals.

Complementary advances may address these gaps. In 2023, Katsuhiko Hayashi's group at Osaka University generated egg cells from male mouse cells, which could supply the needed eggs for Y-CUT. Ishiuchi is also developing a method to insert a second X chromosome to restore typical XX fertility. Separately, researchers have shown that inserting rat chromosomes into mice can create XY males, offering a potential route to produce males from female-only populations.