Scientists create female clones of male mice for first time

Japanese scientists have successfully created female clones from male mice by removing the Y chromosome from male cells. The team, led by Takashi Ishiuchi of the University of Yamanashi and Shogo Matoba of the Riken BioResource Research Center, used a CRISPR-based tool they call Y-CUT to eliminate the Y chromosome, resulting in female pups that were genetically identical to the original males except for the missing chromosome. The findings were shared in a preprint paper on bioRxiv earlier this month and have not yet undergone peer review.

The female clones, which had XO chromosomes instead of the usual XX, grew up healthy and fertile, according to Ishiuchi and Matoba. In additional experiments, the researchers created female clones from cryopreserved male cells, and the cloned males and females were able to mate and produce healthy pups. This suggests the technique could be applied to samples stored in "frozen zoos," which preserve cells and tissues from various animal species.

The work challenges the long-held belief that both sexes are required for reproduction in mammals. Ishiuchi said the team was inspired by the Okinawa rubble goby, a fish that can change sex when necessary. The technique could offer a new tool for rescuing endangered species, particularly in scenarios where only males remain, since standard cloning replicates only the donor's genes and would produce all-male offspring.

Monika Ward, a reproductive biologist at the University of Hawaii who was not involved in the research, called the achievement unprecedented. Ben Novak, lead scientist at the conservation organization Revive & Restore, said he is confident there will be many applications, especially for conservation. The approach could also help produce genetically engineered animals more efficiently, according to Ward.

The Y-CUT method still requires hollowed-out egg cells from females of the same or a closely related species, and it is not useful when only females survive. While XO female mice are fertile, other mammals with XO chromosomes often experience infertility. Ishiuchi is working on inserting a second X chromosome to restore fertility in such cases. In 2023, Katsuhiko Hayashi of Osaka University showed that cells from male mice could be turned into egg cells, a complementary approach that could supply the needed eggs.

Novak noted that a similar technique could help create male clones from female cells, citing recent work by Sayaka Wakayama of the University of Yamanashi that inserted rat chromosomes into mice. That could benefit species like the black-footed ferret, where a recently cloned female is valuable but can produce only a few litters, whereas a male clone could contribute to dozens.