Japanese Scientists Produce 1,206 Clones From One Mouse Over 58 Generations Before Mutations Halt Process
Researchers cloned 1,206 mice over 20 years and found that genetic mutations accumulated until the 58th generation died within days of birth.
New ScientistResearchers in Japan generated 1,206 cloned laboratory mice from a single female donor between 2005 and 2025, and found that the process eventually failed when accumulated genetic mutations proved fatal. The 58th generation of clones died within days of birth despite appearing physically normal.
Developmental biologist Teruhiko Wakayama of the University of Yamanashi, senior author of the study published earlier this year in Nature Communications, said no one has ever continued re-cloning for this long before.
"This is the first time we've discovered that repeated re-cloning eventually reaches its limits," he said. The team repeated the cloning process every three to four months using nuclear transfer, a method first used to produce Dolly the sheep in Scotland in 1996 and Cumulina, the first cloned mouse, in Hawaii in 1998.
A specialized ovarian cell called a cumulus cell was used as the donor nucleus source.
All clones were females with brown fur. Preliminary results covering the first 25 generations were published in 2013 and concluded that re-cloning could likely continue indefinitely. The researchers continued the work for 13 more years and sequenced the genomes of 10 clones from various generations.
Up to the 20th generation, the clones gave birth to about 10 babies per litter when mated with ordinary male mice. After the 20th generation, litter sizes declined. An increase in large-scale harmful mutations, including chromosomal abnormalities such as loss of one X chromosome, began with the 27th generation.
Wakayama said mutations occurred at a rate three times higher than in offspring born through natural mating. "In cloning, all genes are passed on to the next generation, meaning that all defective genes are also passed on," he said. "We had believed that we could create an infinite number of clones," Wakayama said.
The study results, the researchers said, pointed to the importance of sexual reproduction in countering deleterious genetic mutations in mammals. Wakayama said mammals cannot sustain their species through cloning.
