Mouse created without father
Scientists turn egg cell into surrogate
sperm.
21 April 2004
HELEN
PEARSON
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| Kaguya is one sucess
from 460 attempts at growing embryos. |
| © T. Kono |
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From time immemorial, making a mammalian baby has involved
two essential ingredients: eggs and sperm. Now Japanese
scientists have written men out of the reproduction
rule-book, and created fatherless mice.
The team made the animals by combining the nucleus
of one female's egg with that of another, essentially
creating a mouse with two mothers. "It is a bit of a
surprise," says evolutionary biologist David Haig of
Harvard University, Boston.
After nearly 460 attempts at growing embryos, ten live
pups were born and just one of those survived to adulthood.
Christened Kaguya, from the story of a girl discovered
in a bamboo stump, the mouse is now 14 months old and
has babies of her own. She is "very healthy", says team
leader Tomohiro Kono of Tokyo University of Agriculture.
Some might say that Kaguya is living proof of men's
futility, in the baby-making stakes at least. But scientists
maintain it is premature for chaps to step aside in
human reproduction: there are significant obstacles
to transferring the technique to the fertility clinic.
Like human reproductive cloning, which is thought unsafe,
it is not known whether the animals produced are entirely
healthy and normal. The technique is also hugely laborious,
has a high failure rate and would involve genetically
engineering a human egg, which is generally considered
to be ethically unacceptable.
"The popular press will say that men are redundant,"
predicts developmental biologist Azim Surani of the
University of Cambridge, UK. "But what the researchers
did is not straightforward."
Men not included
The process by which a female's egg is triggered to
grow without fertilization is called parthenogenesis.
Although plants, some fish, frogs, insects and occasionally
chickens can all procreate without a partner, until
now mammalian embryos created this way have died halfway
through pregnancy.
This is thought to be because mammalian embryos need
the correct combination of genetic material from mother
and father in order to survive and grow. Although eggs
and sperm carry equivalent sets of genes, they are stamped
with different patterns of gene expression called imprints,
meaning that certain genes are active in eggs and silent
in sperm, and the other way around.
Other researchers have attempted to bypass imprinting
and kick-start parthenogenesis by pricking, shocking
or chemically jolting mouse eggs, without success. But
Kono and his colleagues tried a more subtle approach,
effectively metamorphosing a female egg into a surrogate
sperm, they report in this week's Nature1.
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| Kaguya shows that
imprinting normally blocks parthenogenesis. |
| © T. Kono |
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The researchers started with an immature, female egg
whose genes had not yet been stamped with an imprint.
They took the egg from a mouse genetically engineered
to lack both a gene known as H19, which is normally
subject to imprinting, and a region that would otherwise
switch off a gene called Igf2. The two genes
are thought to control foetal growth.
Kono believes that these steps endowed the egg with
a pattern of gene activity similar to that of a sperm.
They fused this sperm-like egg with another, mature
egg from a different female. By analysing over 1000
genes in the resulting animals, they confirmed that
they were genetically relatively normal.
Experts say the study provides definitive evidence
that it is imprinting that normally blocks parthenogenesis.
The process may have evolved in males to ensure that
reproduction cannot occur without their genetic input,
Kono proposes.
Whether or not this is true, the technique should help
researchers analyse the imprinting process in order
to work out how it controls embryo growth and what happens
when it goes awry. As for Kono, he is already working
on relieving another species of its partner: "The next
target is the pig," he says.
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