All Japanese children know the story of Kaguyahime, the moon princess who was born from a bamboo shoot and refused to marry. Now the fairy-tale girl shares her name with a real-life creature of equally strange origin: the first mammal born from two genetic mothers. Scientists in Japan have created an apparently healthy mouse, which they named Kaguya, by combining the genetic material from two egg cells.
For some animals, it's no trick to develop from a single, unfertilized egg. Insects, reptiles, and others can reproduce this way, a process called parthenogenesis. Mammals, however, require the contribution of both father and mother. In the lab, mammal eggs that are pricked with a needle (apparently simulating penetration by sperm) will begin to divide and can form normal-looking embryos. But the fetuses that develop from such parthenogenetic eggs invariably die in the womb.
Scientists have long suspected that the problem with skipping sperm is that both sets of chromosomes in a parthenote are "imprinted" as female. Imprinting is the process in which certain genes are turned on or off during the development of eggs and sperm. The parthenogenetic embryos then get twice the normal dosage of some genes, and lack others.
To try to circumvent this problem, developmental biologist Tomohiro Kono of Tokyo University of Agriculture and his colleagues tried to make a set of chromosomes from a mouse egg as sperm-like as they could manage. They did this by collecting DNA from an immature oocyte, which the team suspected lacked maternal imprints. Because sperm imprint fewer genes than eggs, these imprint-free oocytes' DNA more closely resembles a paternal rather than a maternal genome. To further simulate a paternal genome, the team used immature oocytes that carried a mutation that disables a gene implicated in a cascade of imprinting events thought to derail parthenote development.
The team transferred these male-like chromosomes into a mature oocyte that had its own copy of chromosomes, creating a full genome. Next, they transferred the chromosomes to a third oocyte, which has had its nucleus removed, and then chemically prompted that oocyte to begin dividing. Kaguya is the product of one of these reconstructed eggs, and in the 22 April issue of Nature, the team reports that she has survived to adulthood and given birth to a litter of healthy pups.
The experiment is a "proof of principle" that a mammal can be born without contribution from sperm, says Patrick Tam of the Children's Medical Research Institute in Sydney, Australia. However, some scientists question whether Kaguya can really be called a parthenote, because she has two genetic parents, albeit both female. In any case, men don't need to fear becoming redundant anytime soon, says Tam. "There are not more than two or three labs in the world capable of pulling this off."
Kono's team's Nature paper