Repeated Cloning Leads to Fatal Genetic Mutations in Mice

Researchers have discovered that repeated cloning of mice for two decades leads to severe genetic mutations that accumulate over generations and ultimately become fatal. This research identifies critical limitations of current cloning technology.

The study, conducted in Japan from 2005 to 2025, involved generating 1,206 cloned laboratory mice from a single female donor. While no outward issues were observed through the first 25 generations, mutations subsequently began to accumulate, becoming fatal. The 58th generation of clones, despite having no visible physical abnormalities, died within days of birth.

Key Findings

• The research contradicts the previous notion that clones are identical copies of the original donor animal.
• It disproves the idea that cloning using current technology can be carried out indefinitely without adverse effects.

Teruhiko Wakayama, a developmental biologist at the University of Yamanashi and senior author of the research, published in Nature Communications, stated that mutations occur at a rate three times higher than in offspring born through natural mating.

• This accumulation of mutations prevents mammals from sustaining their species through cloning, clarifying why mammals, unlike plants and lower animals, cannot maintain their species through this method.

Research Process and Observations

Cloning was repeated every three to four months, with each generation cloned from the preceding one. All clones were females with brown fur, matching the original donor.

Preliminary results published in 2013, covering the first 25 generations, had indicated the clones were healthy. Wakayama noted that this earlier conclusion was revised after 13 additional years of research and genetic sequencing.

Genomes of 10 clones from various generations were sequenced. The process was likened to duplicating a picture multiple times, where quality deteriorates with each copy.

The study results suggest the importance of sexual reproduction in countering deleterious genetic mutations in mammals.

Fertility and Method

Fertility tests showed that clones up to the 20th generation produced about 10 babies per litter, similar to naturally reproducing female mice. Beyond this, clones began having smaller litters, reflecting the accumulating mutations.

The researchers used nuclear transfer technology, the same method employed to produce Dolly the sheep in 1996 and Cumulina the mouse in 1998. This technique involves transferring the nucleus from a donor cumulus cell into an egg cell whose own nucleus has been removed.

Genetic Impact

Harmful, large-scale mutations, including chromosomal abnormalities such as the loss of one X chromosome, became evident starting with the 27th generation.

In cloning, all genes, including defective ones, are passed on to the next generation, contributing to the accumulation of these issues.