Science: Mice Created without Fathers

Society | April 23, 2004, Friday // 00:00

By http://news.bbc.co.uk

Scientists have created two female mice without fertilising the eggs they grew from, the journal Nature says.

The eggs had two sets of chromosomes from two female mice, rather than one from the mother and one from the father as in a fertilised embryo.

The phenomenon, called parthenogenesis, never occurs naturally in mammals.

Some researchers say the procedures may be applied to stem cell research, but the scientists who carried out the work say it would not yet work in humans.

Tomohiro Kono and colleagues switched off a key gene in the donor eggs which affected imprinting - a barrier to parthenogenesis in mammals. "Insects can reproduce by parthenogenesis. Even chickens can be made to reproduce by parthenogenesis. I wanted to find out why mammals are different," Dr Kono of Tokyo University of Agriculture, Japan, told BBC News Online.

The team injected the genetic material from immature mouse eggs into mature eggs with their own set of chromosomes. They then "activated" the combined eggs, prompting them to start growing as an embryo.

By blocking expression of a gene called H19 in the immature mouse eggs, the researchers increased the activity of another gene called Igf2.

Igf2 manufactures a protein responsible for regulating growth in the developing foetus.

These genes are said to be imprinted. Imprinting means that some genes are working in maternal DNA but switched off in paternal DNA, or vice versa. They are unequally expressed. The genetic manipulation carried out by the researchers gave the genes a more paternal character.

But as a result of this modification, just two out of 598 mice embryos made it to full term. "The efficiency of this technique is rather low. So it's not a technique that can be readily adapted for practical purposes," Professor Azim Surani, an expert in imprinting at the University of Cambridge, UK, told BBC News Online.

One of the surviving mice was used for testing, while another, which the researchers named Kaguya after a Japanese fairy tale character, was allowed to grow into an adult.

"To me it is striking that a relatively simple genetic modification, where they took away the gene and its regulatory sequences, allowed these embryos to develop," Marisa Bartolomei, associate professor at the University of Pennsylvania, US, told BBC News Online.

Researchers were quick to head off suggestions that the technique could play a role in fertility treatment, at least for the moment. And it is not even known whether it would work in humans. "This is a very complicated thing. So no. Impossible to do this experiment in a human. And I don't want to do it," said Dr Kono.

However, some researchers said that the procedures could - in theory - have applications in stem cell research. Dr Bartolomei suggested that making embryos without the need for fertilisation might allow researchers to circumvent political and ethical obstacles to using stem cells.

"I would expect that just because it's parthenogenetic, the public wouldn't discriminate between that and the more traditional way of doing it," said Dr William Colledge of the University of Cambridge. Professor Surani commented: "Parthenogenetic stem cells were made many years ago. This latest procedure is a very complicated one and it's not necessary for stem cell research."

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