A
mammal that is the daughter of two female parents has been created for the
first time.
Until
now such a feat had been considered biologically impossible. But the mouse,
called Kaguya, was born without the involvement of any sperm or male cell -
only female eggs were needed.
In the
same way that the birth of Dolly the sheep in 1997 shattered the dogma that
an adult cell could never be reprogrammed to make a new individual, the fact
that Kaguya lives challenges another one of long-held rule: that two mammals
of the same sex cannot combine their genomes to give rise to viable
offspring.
What
scientists learn from this remarkable rodent, created in Japan, is likely to
have an impact on fields from fundamental embryology to assisted reproduction
and even cloning.
However,
several experts have already warned against assuming the method could be used
in humans to help two women have a biological child, not least because the
process is extremely inefficient.
It
would also be highly risky and require a very large number of eggs. "To
do this kind of experimentation in humans would be outrageous," says
fertility specialist Gianpiero Palermo of Cornell University in New York.
Virgin birth
Kaguya
was created by combining the genetic material of two egg cells. This would
not normally work, a fact evidenced by decades of studies into the phenomenon
of parthenogenesis, also known as virgin birth.
In
parthenogenesis, the egg becomes the sole source of genetic material for the
creation of an embryo. It is a mode of reproduction in some species, though
not in mammals. In mammals parthenogenesis can begin if an egg is
accidentally or experimentally activated as if it had been fertilised - but
this parthenote never grows past a few days.
This is
because of there a biological phenomenon known as imprinting. During sperm
and egg formation in mammals, certain genes necessary for embryo development
are shut down with a series of chemical marks, or imprints, some in the
sperm, other in the egg. Only when sperm and egg meet are all of the key
genes available, allowing proper development.
But
Tomohiro Kono and colleagues at the Tokyo University of Agriculture in Tokyo,
Japan, circumvented this imprinting barrier by manipulating the nucleus of a
female egg to make it more male-like.
This
was far from simple. Perhaps the most important of the many steps required
was the creation of eggs that produced a protein called IGF-2. This is
crucial to embryo growth but is normally only produced by sperm-derived DNA.
The researchers achieved the trick by using genetically altered mice to
provide the donated eggs.
The
nucleus of such an egg was then transferred into a regular egg that, with the
genomes of two females, proceeded to grow and divide. However, Kaguya and one
sister were the only live animals resulting from 457 reconstructed eggs.
Fertility techniques
Although
attempting to apply such an approach to humans horrifies experts, that does
not mean the technique will not have a big impact in studies of human
biology. For example, future experiments of the same kind will allow
scientists to learn which other genes can be altered to bypass imprinting
defects.
This
could help optimise fertility techniques, some of which are thought to
interfere with imprinting. In addition, the work might provide new hints to
make animal cloning more efficient, as many of the failures in cloned animals
are thought to come from imprinting defects.
While
he agrees the creation of the mouse is a major achievement, imprinting expert
Azim Surani, at the University of Cambridge, UK, hopes the work will not be
misinterpreted to imply that males are somehow redundant.
"It
shows the opposite - clearly IGF-2 is the key gene," he says. "They
managed to get around it but to really get to a situation where the procedure
would work as well as [fertilisation with] sperm, you would need to mutate a
lot more genes."
Journal
reference: Nature (vol 428, p
860)
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