CLONING HAS made Dolly the sheep an international superstar, but the technique may not work for everybody. This week, U.S. researchers have announced that some animals may be genetically `unclonable.'
Their finding in mice suggests that plans to clone endangered species, for instance, might fall flat if the remaining animals don't have clone-friendly genes. ``The possibility of a genetic block against this technique could have some serious repercussions,'' says William Rideout of the White-head Institute for Biomedical Research near Boston.
Sheep, mice, cows and goats have all been successfully cloned using the technique of nuclear transfer, where the nucleus of a donor cell is implanted into an egg stripped of its own genetic material. A key step in the cloning process is believed to be the `reprogramming' of the donor nucleus by the egg, an unknown mechanism by which the developmental clock of the nucleus is reset to an embryonic state.
By that logic, embryonic stem cells - which develop into the foetus in a natural embryo - should be ideal candidates for the donor cells because they would need very little reprogramming. So Rideout and his colleagues, including the Hawaiian team who first cloned mice, tried to make clones using embryonic stem cells from different mouse strains. Using stem cells created by mating two different strains of mice, called 129SvJae and C57BL/6, the researchers produced seven live animals from 227 nuclear transfer embroys - an efficiency of 3 per cent, which is considered quite high. But they were unable to get any live births from the 418 embryos created from stem cells derived from one of the parent strains, 129SvJae. Rideout's team is now exploring two explanations. The first is that certain genes in the 129svJae donor nucleus that are essential for reprogramming it are not active enough. Mating would cure this problem by bringing in more robust copies of those genes to compensate.
The second possibility is that inbreeding of the 129SvJae strain caused the cloning barrier. This means the maternal and paternal chromosomes in these cells are nearly identical, which Rideout suggests may confuse the cell about how to process the chromosomes. Steve Stice, a biologist who clones cows at the University of Georgia in Athens, says his team has suspected that some cows are difficult to clone. But the phenomenon was never pinned down. ``Mouse genetics is so much more advanced, they should be able to figure out why this happens,'' he says.
Whatever the answer turns out to be, Riedout thinks it might provide lessons for all cloners. The genetic factors that limit 129SvJae's clonability could also limit cloning efficiency in many animals. If these factors could be identified, it might be possible to find ways to prevent them causing problems in donor cells, making cloning any animal far easier
- New Scientist