[Serial cloners of Yamanashi]

Area of Science:

• Reproductive biology
• Genetics
• Mammalian cloning

Background:

• Nuclear transfer (NT) is a technique for cloning mammals.
• Serial cloning aims to produce multiple generations from a single genetic source.

Purpose of the Study:

• To assess the long-term viability and genetic stability of mice produced through serial nuclear transfer.
• To investigate the genetic consequences of repeated cloning over many generations.

Main Methods:

• Serial cloning of mice using nuclear transfer over approximately 20 years.
• Phenotypic analysis of successive generations.
• Molecular analysis to detect genetic variations, including point mutations and structural variants.

Main Results:

• Successful cloning up to the 57th generation, with increasing difficulty observed after the 25th generation.
• Progressive accumulation of a significant number of point mutations and structural variants in later generations.
• Evidence of declining genetic integrity with successive cloning.

Conclusions:

• Serial nuclear transfer leads to the accumulation of detrimental genetic alterations.
• The study underscores the limitations of cloning for maintaining long-term genetic fitness.
• Sexual reproduction is essential for purging deleterious mutations and ensuring the evolutionary fitness of species.