Mammals can be cloned up to 25 times before things start to go wrong, at least in mice

Embargoed until: Publicly released: 2026-03-25 03:00

International

Photo by Matthew Mejia on Unsplash

Mammals can not be repeatedly cloned indefinitely, according to an international study in mice, which found that after 25 generations of repeated cloning, DNA mutations that would normally be repaired through natural mating began to accumulate, and after 57 generations, the offspring did not survive. The researchers serially cloned mice over 20 years, finding that early generations were healthy and did not have large-scale DNA mutations, while later generations accumulated DNA mutations that resulted in a rapid decline in birth rate after the 40th generation. However, they also found that when re-cloned mice from near the final generation were mated with males naturally, a few of their embryos developed to full term, which the authors say suggests that mammals rely on sexual reproduction to eliminate the genetic anomalies that may be caused by asexual reproduction.

News release

From: Springer Nature

Genetics: Limitations of repeated cloning in mice *VIDEOS*

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 27^th 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 40^th 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.

Multimedia

A G56-generation re-cloned mouse. It has grown into a healthy adult.

Nuclear transfer

Journal/
conference: Nature Communications

Research:Paper

Organisation/s: University of Yamanashi, Japan

Funder: This work was partially funded by the Research Fellowships of Japan Society for the Promotion of Science to D.I. (JP20J23364), A.U. (24K03096, 24H02061, 24H00752), S. W. (23K08843) to T.W. (23K18124 and 24K01779); the Naito Foundation and Takahashi Industrial and Economic Research Foundation (189) to S.W.; Asada Science Foundation and the Canon Foundation (M20-0008) to T.W.

Media Contact/s

Contact details are only visible to registered journalists.