Limitations of serial cloning in mammals

Mammals can now be cloned artificially, but it remains unknown whether they can also maintain their species through cloning. Herein, we continued serial cloning for 20 years from a single donor mouse. These re-cloned mice appeared normal and had normal lifespans, but large structural and lethal mutations accumulated in their DNA with each generation. The birth rate of serial cloning began to decline from the 27th generation, and the 58th generation was the last. When re-cloned mice from near the final generation were mated with males, their oocytes could be fertilized, but most embryos degenerated. However, a few embryos were normalized by meiosis and fertilization and developed to full term, suggesting that mammals rely on sexual rather than asexual reproduction to eliminate genetic anomalies caused by clonal reproduction. Here they show that extended serial somatic cell cloning imposes a threefold increase in de novo mutations compared to natural reproduction, progressively reducing birth rates and ultimately limiting clonal propagation to 58 generations.