Sex becomes a setting in cloning: a CRISPR cut makes female clones of a male mouse

Takashi Ishiuchi's group at the University of Yamanashi, working with Shogo Matoba at the RIKEN BioResource Research Center, reports deleting the Y chromosome from cloned male mouse embryos with a CRISPR tool and obtaining healthy, fertile female mice otherwise genetically identical to the donor male ^[1][2][4][7]. Sex is now a variable that can be set during a cloning run, which is the difference between a tissue bank holding one male you can copy and one you can breed from ^[3][10].

The procedure is standard somatic cell nuclear transfer with one added step. The team put DNA from the blood cells of a male mouse into mouse eggs whose own DNA had been removed, treated some of the resulting embryos with a CRISPR-based tool they call Y-CUT, and transferred the embryos to surrogate mothers ^[5]. Every mouse born from a Y-CUT embryo was female, genetically identical to the donor father apart from the missing Y; the untreated embryos all produced male clones ^[6]. Matoba calls the result "dual-sex cloning" ^[7]. The clones bred with each other and produced offspring that appeared healthy, alive for more than a year with no clear defects, which Matoba describes as sexual reproduction initiated from a single male genome ^[8]. Ishiuchi's framing is blunter: remove the Y immediately after fertilisation and "it is essentially sex reversal" ^[2].

XO females had turned up in mouse cloning before, by accident, when the Y happened to be lost ^[9]. What is new is doing it on purpose with a tool the authors describe as reliable ^[4]. The delivery route matters as much as the edit. An earlier study produced both male and female clones from a male mouse embryonic stem cell line, but by a method unlikely to work in other species, whereas nuclear transfer has already been applied in many mammals and accepts living or stored donor material ^[13]. The idea came from fish that switch sex, including the Okinawa rubble goby, to keep sexual reproduction going ^[16].

Two constraints sit on the conservation pitch. The first is chromosome tolerance: an XO mouse is healthy and fertile, but that is not true across species, and Linda Penfold of SEZARC says Y-deleted offspring are infertile in humans and horses and that this is likely in multiple wildlife species; she also raises ethical concerns about producing Y-deleted animals ^[14][15]. The second is arithmetic. If both parents are clones of the same male, the offspring's nuclear genome traces to one founder, so the technique restarts reproduction without adding genetic diversity ^[1].

What to watch is whether Y-CUT survives contact with a second species. Teruhiko Wakayama, at Yamanashi but not part of the study, says it would be incredibly valuable if it worked outside mice ^[11]. Ben Novak of Revive & Restore, which has worked on cloning Przewalski's horse and the black-footed ferret, says the group is laying foundations for chromosome manipulation that will matter in many conservation cases, and agrees the method suits frozen samples from only one or two individuals ^[12]. Also worth noting what this reporting does not contain: no livestock application, no regulator, and no approval pathway, with the only governance objection on record being Penfold's ethical one ^[2]. A technique that sets sex ratio at the embryo stage will not stay confined to endangered species, but nothing in the published account addresses that use yet ^[2].