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CLONING has made Dolly the sheep an international superstar, but the
technique may not work for everybody. This week, researchers in the US have
announced the surprising discovery that some animals may be genetically
鈥涡苍肠濒辞苍补产濒别鈥�.

Their finding in mice suggests that plans to clone endangered species, for
instance, might fall flat if the remaining animals don鈥檛 have clone-friendly
genes. 鈥淭he possibility of a genetic block against this technique could have
some serious repercussions,鈥� says William Rideout of the Whitehead 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 鈥渞eprogramming鈥� 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鈥攚hich develop into the fetus in a
natural embryo鈥攕hould 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. 鈥淲e didn鈥檛 expect it, but we found
tremendous variability,鈥� says Rideout.

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 embryos鈥攁n 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鈥檚 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. 鈥淢ouse genetics is so much more advanced,
they should be able to figure out why this happens,鈥� he says. 鈥淭hat will be very
颈苍迟别谤别蝉迟颈苍驳.鈥�

Whatever the answer turns out to be, Rideout thinks it might provide lessons
for all cloners. The genetic factors that limit 129SvJae鈥檚 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.

Ian Wilmut, head of the team that created Dolly at the Roslin Institute in
Edinburgh, says the findings are important. 鈥淣ot everything will be clonable
with any particular method,鈥� he agrees. He鈥檚 hopeful that this will change in
future. 鈥淎s time goes on nuclear transfer techniques have improved rapidly, and
I鈥檇 guess that there may one day be ways of cloning anything.鈥�