Researchers in Japan have produced 26 successful generations of cloned mice from a single individual. That's a total of 598 mice, all of whom are essentially genetic duplicates. The achievement was made possible by a new cloning technique that allowed researchers to overcome genetic degradation problems characteristic of generational re-cloning. The breakthrough shows that mammalian cloning lines can be extended and reproduced without limit.
Indeed, animal re-cloning (i.e. cloning a clone) works great, but up to a point. Eventually, over the course of several generations, a clonal line will ultimately fail, the result of accumulated lethal genetic and epigenetic abnormalities. But the Japanese researchers devised a crafty biohack that appears to remedy this problem.
The new technique, developed by Teruhiko Wakayama of the RIKEN Center for Developmental Biology in Kobe, Japan, was so successful that it resulted in well over two dozen generations of re-cloned mice. Moreover, the cloning efficiency did not decrease over the course of those generations, and the project was allowed to continue indefinitely (and in fact, the project is still going!). In all, nearly 600 viable offspring were produced from a single donor mouse. The experiment started seven years ago and it is considered the largest cloning project using a mammal to date.
Wakayama and his team achieved this by using the standard cloning technique, somatic cell nuclear transfer (SCNT), and adding a histone deacetylase inhibitor (trichostatin), and other chemicals to the process.
In SCNT, the nucleus of a somatic cell is transferred to the cytoplasm of an egg that has had its nucleus removed (an enucleated egg). Once inside the egg, the somatic nucleus is reprogrammed to become a zygote nucleus, what is really a fertilized egg.
But as noted, this can’t be done indefinitely, as genetic problems start to creep in over successive generations. But adding the HDI to the mix seemed to do the trick. It's a class of compounds that interfere with the function of histone deacetylase, a class of enzymes that allow histones (proteins that package and order the DNA into nucleosomes) to wrap DNA more tightly. They can also be used to alter gene expression.
According to the researchers, the cloned mice had normal biological features, including regular lifespans and reproductive capabilities. That said, genetic analysis did show some minor abnormalities, including an oversized placenta. But none of these characteristics had a detrimental impact on the line’s clonal health. The researchers noted that “serially recloned mice have the same characteristics as standard clones.”
Their results show that repeated iterative re-cloning is possible. The researchers wrote that “with adequately efficient techniques, it may be possible to re-clone animals indefinitely.”
Once refined, the technique could result in the large-scale production of cloned animals for farming or conservation purposes. Moreover, animals can continue to be cloned long after the source individual has died.
Check out the entire study at Cell Stem Cell.
Supplementary source: AFP.