CRISPR Y-CUT Turns Male Mice Into Female Clones

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- Takashi Ishiuchi at the University of Yamanashi and colleagues at RIKEN developed Y-CUT, a CRISPR-based tool that reliably eliminates the Y chromosome from male mouse embryos created via somatic cell nuclear transfer (male blood-cell DNA inserted into eggs stripped of their own DNA).
- Y-CUT–treated embryos produced only female clones (XO, genetically identical to the father minus the Y chromosome), while untreated embryos from the same protocol produced only male clones — a process the team calls 'dual-sex cloning.'
- Shogo Matoba at RIKEN said the resulting female clones were fertile and, when mated together, produced healthy offspring that have survived over a year with no clear defects, demonstrating that 'sexual reproduction was initiated from a single male genome.'
- Revive & Restore's Ben Novak, whose group has cloned Przewalski's horse and black-footed ferret, said the work 'lays the foundations for a future of manipulating chromosomes that is probably going to be important in many cases for conservation,' particularly for frozen tissue from extinct or near-extinct species.
- SEZARC's Linda Penfold pushed back, noting Y-deleted XO females are not fertile in humans or horses and likely in many wildlife species, warning of genetic-diversity collapse if entire populations are bred from a single cloned animal.
- Ishiuchi acknowledged the fertility limitation but pointed to research showing the drug Reversine can coax XO cells to gain a second X chromosome, suggesting Y-CUT plus Reversine could extend fertile female cloning to more species.
Why it matters: The technique offers a potential last-resort lifeline for species reduced to a single surviving male — or, more realistically, to frozen tissue in cell banks — but conservation biologists stress it is no substitute for habitat protection. Linda Penfold explicitly warned that XO females are infertile in humans and horses, meaning real-world deployment depends on pairing Y-CUT with follow-up work like Reversine-based chromosome repair.
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