Generation 20 of a single mouse (Image: Cell Stem Cell)

A mouse has smashed the record for sequential cloning – the ability to make clones of clones of clones. Now the laboratory behind the feat will attempt to make clones from cells extracted from mouse fur, stuffed bodies and excrement.

Teruhiko Wakayama at the RIKEN Center for Developmental Biology in Kobe, Japan, who carried out the work, says the technique could help in producing high-quality animals for farms and conservation purposes. “If a ‘super cow’ that could produce a lot of milk or Kobe beef could be cloned at low cost, then not only consumers but also farmers would be happy,” he says.

Twenty-five generations of clones have come from the mouse, and all 580 of them were healthy, lived normal lifespans and could have healthy pups through normal mating.


In 2008, Wakayama’s team produced clones from dead mice that had been frozen for 16 years. “My lab is now trying to make cloned mice from fur, stuffed bodies, and excrement,” says Wakayama.

Third-generation clone

Enthusiasm for therapeutic cloning, as the technique that led to Dolly the sheep is known, waned in the mid-2000s following scientific fraud scandals in South Korea and the difficulty of producing animals without abnormalities. Researchers struggled to produce cloned cattle, pigs, cats and dogs beyond two or three generations.

Now Wakayama’s team has emphatically broken through this barrier thanks to a chemical which more faithfully resets the cell nucleus to be cloned back to an embryonic state.

First, the team emptied a mouse egg cell of its nucleus. Then they inserted a nucleus from the adult mouse to be cloned before putting this cell into a bath of an enzyme blocker called trichostatin. The resulting embryos – all females – had fewer abnormalities in their histones, the packing materials for chromosomes.

Previous studies had identified faulty histones in cloned embryos as a possible reason for the poor success rate of cloning, as well as clone abnormalities. A possible explanation for the previous limit on the number of “reclones” is a build up of such abnormalities over successive generations.

Game changer

“So far, nobody has been able to explain the reason for this,” says Wakayama. “We thought that this limitation was caused by the accumulation of genetic or epigenetic abnormalities.”

“This is very impressive work. If this translates to other mammalian species – including humans – it could be a major game changer,” says Robert Lanza, chief medical officer at Advanced Cell Technology, a company based in Marlborough, Massachusetts, that is developing treatments based on stem cells.

Wakayama says he doesn’t know if his technique will make it easier to clone primates, let alone humans, and has no plans to try. “I am a mouse researcher and have no experience with other species. I will not even attempt to use rats, because male rats are extremely difficult to clone.”

One application of cloning is to preserve endangered species, as advocated late last year by Brazil. The ability to make clones from fur, specimens preserved in museums and excrement would potentially allow the “resurrection” of extinct animals.

Journal reference: Cell Stem Cell, DOI: 10.1016/j.stem.2013.01.005