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Mice Created With Two Genetic Moms, No Dad


Births mark first time male's DNA has been cut out of reproduction processApril 21, 2004

Just ahead of Mother's Day, scientists have found a way to cut dads out of the picture, at least among rodents: They have produced mice with two genetic moms — and no father.

It is the first time the feat has been accomplished in mammals.

Scientists said the technique cannot be used on people, for reasons both technical and ethical. In fact, one of the mouse mothers was a mutant newborn, whose DNA had been altered to make it act like a male's contribution to an embryo.

But the new work sheds light on why people, mice and other mammals normally need a male's DNA for reproduction, and some experts say it also has implications for the idea of using stem cells to treat disease.

The feat 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 healthy.

Some lizards and other animals reproduce with only maternal genes, but mammals do not.

Kono, in an e-mail, said the new technique might be useful with animals for agricultural and scientific purposes. When asked if he saw any reason to produce humans this way, he dismissed the question as "senseless."

Experts said ethical concerns and current technology would pose barriers to duplicating the technique in people. For one thing, scientists do not know how to create the precise DNA mutation in humans. Experts also noted that it took hundreds of eggs to produce just two mice and that the health risks are unknown.

However, the study provides new evidence for the standard explanation for why mammals normally need a male's DNA.

Scientists say that in an embryo, some mammal genes behave differently if inherited from the father rather than the mother, and that this 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 is 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 had 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 has not yet taken on the full "female" 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, an array of other imprinted genes had also somehow taken on their normal levels of activity, as if there had been a standard fertilization. The researchers said they do not know how that happened.

Gerald Schatten, a stem cell researcher at the University of Pittsburgh School of Medicine, said the work shows that scientists need to thoroughly understand imprinting in human embryonic stem cells, which are recovered from early embryos. Otherwise, such cells might behave abnormally when used for treating diseases like diabetes or Parkinson's, he said.

Some scientists hope to produce human stem cells by stimulating unfertilized eggs.

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 healthy, fertile mouse can be produced without a father's DNA, he said, that gives hope that stem cells from a similar process would behave normally.

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