Genetics: Limitations of repeated cloning in mice (Nature Communications)
25 March 2026
Repeated cloning cannot be sustained indefinitely in mammals, according to a 20-year study in mice published in Nature Communications. The results suggest that sexual reproduction is necessary to eliminate large-scale genetic mutations that can accumulate in mammalian clones.
Whole animal cloning has been a valuable tool for research, but the low success rates have limited its utility. While some animals and plants can reproduce asexually without accumulating genetic defects, it is not clear whether mammalian cloning could achieve the same. Teruhiko Wakayama and colleagues have previously shown that serial cloning — where a mouse is cloned and the clones are then cloned again — can be performed for up to 25 generations without affecting the health of the offspring. Whether there is a limit to this ability has not been determined.
Wakayama and colleagues continued their experiments to show that serially cloning mice over 20 years eventually leads to accumulation of lethal DNA mutations, which affects birth rates after the 27th generation. Mice could continue to be cloned up to 57 generations without impacting lifespan, but the final generation did not survive after birth. Early generations were healthy and genome sequencing did not detect large-scale DNA mutations. However, DNA mutations accumulated in later generations and correlated with the rapid decline in birth rate after the 40th generation. Cloning also alters the structure of the placenta, which has been observed previously and was confirmed in all-generation clones. When late-generation cloned mice mated naturally, their grand-offspring had normal placenta formation and improved fertility, suggesting that natural mating is important for maintenance of genomic integrity.
The authors suggest that repeated cloning beyond 25 generations leads to accumulation of DNA mutations that would normally be repaired through natural mating. These findings help to improve our understanding of the technological limit of mammalian cloning and provide insight into the DNA repair function of natural mating.
- Article
- Open access
- Published: 24 March 2026
Wakayama, S., Ito, D., Inoue, R. et al. Limitations of serial cloning in mammals. Nat Commun 17, 2495 (2026). https://doi.org/10.1038/s41467-026-69765-7
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