Kaguya Has Two Moms

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In Japanese legend, Kaguya was a beautiful princess who came from the moon and was born inside a bamboo stalk. Today, at the Tokyo University of Agriculture, Kaguya's namesake is a 14-month-old mouse whose conception is every bit as fantastic: she was created by scientists using two eggs and no sperm. As reported in the journal Nature last week, that makes Kaguya the first mouse born by parthenogenesis (from the Greek for virgin birth), a reproductive method seen in insects and reptiles but never before in mammals.

For the moment, Kaguya's creation is a brilliant piece of science with little or no application to humans. The process by which she was produced is so technically difficult — not to mention ethically charged — that it is hard to see how it could be attempted with human subjects. In theory, the technique might be used to create stem cells, but even this scenario is a bit farfetched. What the experiment offers, however, is a tantalizing glimpse into one of the central mysteries of mammalian biology: Why do we need genes from both a mother and a father in order to be born?

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After all, a queen bee's eggs can create male drones without being fertilized, and whiptail lizards are famous among biologists and nature-show hosts for not needing males to reproduce. What makes us different?

The answer, most scientists suspect, has to do with a peculiar process called parental or genomic imprinting, which seems to occur only in mammals. Biologists have discovered subtle changes that are made to about 100 genes and that make a mammalian DNA molecule distinctly male or female. How does a cell know which form to imprint on its DNA? It checks out the surrounding microscopic environment to see if it seems more male-like or female-like.

All other things being equal, an embryo must have both a maternal genomic imprint (usually from an egg) and a paternal genomic imprint (usually from a sperm), or it won't grow properly. If it has two paternal imprints, the placenta grows but not the embryo. If it has two maternal imprints, the embryo grows but not the supporting placenta. Defects in imprinting in humans are thought to contribute to such neurodevelopmental ailments as Prader-Willi syndrome and perhaps some forms of autism. Genes that have lost their imprinting have also shown up in brain tumors.

What a team of researchers led by Tomohiro Kono at the Tokyo University of Agriculture did was create a genetically modified strain of mice in which the females produce eggs with an imprint that is somewhat father-like. Then, in a key step, the team extracted immature eggs from the newborn mice of this strain. Why is this important? The immature eggs had the most paternal imprint of all because they had not yet had time to sense that they were living in a female. By fusing these father-like eggs with normal, mother eggs, the Japanese researchers were able to create an organism that could develop and grow.

It wasn't easy. After nearly 600 attempts, only two baby mice (known as pups) survived. One was sacrificed for genetic analysis. The other, dubbed Kaguya, grew up, mated the usual way and produced two litters. Despite the fact that Kaguya bore offspring, "we really don't know how healthy she is," says Marisa Bartolomei, an imprinting expert and Howard Hughes investigator at the University of Pennsylvania.

But scientists now have a better understanding of the biological underpinnings of procreation. "In spite of all the differences between men and women — our fights, arguments and seeming incompatibility — at the end of the day you still need a set of male and female genes for the species to go on," Kono says. "I find that fascinating."