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Scientists conceive mouse with two moms
Updated: 2004-04-22 09:10

Men, your gender just took a hit in the animal kingdom. Scientists report they've created mice by using two genetic moms -- and no dad.

That's a first for any mammal. But don't look for this service at the corner fertility clinic. Experts say the mouse procedure can't be done in people for technical and ethical reasons.

In fact, one of the moms was a mutant newborn, whose DNA had been altered to make it act like a male's contribution to an embryo.

The work sheds light on why mice and people normally do need a dad's DNA to reproduce. Some experts also said it held implications for using human stem cells to treat disease.

The achievement is reported in Thursday's issue of the journal Nature by Tomohiro Kono of the Tokyo University of Agriculture in Japan, with colleagues there and in Korea. They say they produced two mice, one of which grew to maturity and gave birth. Kono said this mouse, named "Kaguya" after a Japanese fairy tale character, appears to be perfectly healthy.

Kono, in an email, said the procedure might be useful with animals for agricultural and scientific purposes. When asked if he saw any reason to produce human babies this way, he dismissed the question as "senseless."

Some lizards and many other animals reproduce with only maternal genes, but mammals do not. Lab experiments in mice had produced embryos and fetuses, but no successful births.

Such development is enough to produce stem cells, however. Some researchers hope that by stimulating unfertilized human eggs to develop into what they call "parthenotes," they can harvest stem cells without destroying ordinary embryos. Researchers hope stem cells can be used to treat a variety of diseases.

Kent Vrana, a researcher at Pennsylvania State University who is studying the unfertilized-egg approach, said the Nature study is encouraging for that technology. If a normal, fertile mouse can be produced without a father's DNA, he said, that gives hope that stem cells from a similar process would be normal as well.

The Tokyo work provides new evidence for the standard explanation for the developmental roadblock. Scientists say some mammal genes inherited from the father behave differently in the embryo than if they came from the mother, and that paternal activity pattern is needed for normal development.

Relatively few genes act in that way, and they are said to be "imprinted." In some cases these genes are active only if inherited from the father, not the mother, and in other cases it's the other way around.

For the study described in Nature, the researchers got around the need for male-derived DNA by turning to mutant mice. The female mice were missing a chunk of DNA, and as a result, two of their genes would behave in an embryo as if they'd come from a male.

What's more, the scientists took this mutated DNA from the egg cells of newborns, because at such a young age the DNA hasn't yet taken on the full "female" pattern of imprinting seen in mature eggs.

That DNA was combined with genes from ordinary female mice to make reconstructed eggs. Only two of 457 such eggs produced living mice.

Marisa Bartolomei, who studies imprinting at the University of Pennsylvania School of Medicine, said she was "stunned" that manipulating just the two genes removed the roadblock to producing live mice.

In fact, analysis showed that an array of other imprinted genes had somehow taken on their normal levels of activity, as if there'd been a standard fertilization. The researchers said they don't know how that happened.

Gerald Schatten, a stem cell researcher at the University of Pittsburgh School of Medicine, said the work emphasizes that scientists must thoroughly understand imprinting in human embryonic stem cells. Otherwise, such cells might behave abnormally when used for treating diseases like diabetes or Parkinson's, he said.

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