October 8, 2007 / 5:42 PM / 10 years ago

'Designer mice' used by scores of researchers

<p>Oliver Smithies, Ph.D., of the University of North Carolina at Chapel Hill School of Medicine, a co-recipient of this year's Nobel Prize in Medicine or Physiology, listens to a question during a news conference at the Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina October 8, 2007. Smithies shares the award with two other scientists, Mario R. Capecchi of the University of Utah, and Martin J. Evans of Cardiff University in Wales.Chris Keane</p>

WASHINGTON (Reuters) - The gene-targeting technique that helped scientists create "designer mice" is used by scores of labs across the world and has helped pin down the function of 10,000 different genes.

Three researchers won the 2007 Nobel Prize in Medicine or Physiology on Monday for their work, which was done separately but when taken together made possible the "knockout" mice that are now key to basic medical research.

Martin Evans of Britain's Cardiff University laid the groundwork by discovering and isolating embryonic stem cells in mice -- the master cells that make up a days-old embryo and which give rise to an entire living animal.

Evans figured out how to genetically tinker with the cells and implant these altered embryos into foster mothers, which gave birth to mice with the desired genetic changes.

Mario Capecchi of the U.S. Howard Hughes Medical Institute and the University of Utah and Oliver Smithies of the University of North Carolina independently developed precise ways to disable, or knock out, a single chosen gene.

Scientists have used their techniques to genetically modify mice with human conditions such as cancer, heart disease, Alzheimer's disease, cystic fibrosis and high blood pressure.

"It is now being applied to virtually all areas of biomedicine, from basic research to the development of new therapies," the Nobel Foundation wrote in its statement on the prize.

MISSING FINGERS

Capecchi said scientists had developed the means to alter any gene in the mouse genome.

"What that allows you to do is to then evaluate what happens," he said in a telephone interview.

"If for example, you see a little finger disappear, then you know that gene is important for making little fingers. That way you can infer what the function of any gene is."

<p>Martin Evans poses in this undated handout photograph taken at Cardiff University. Evans, a professor of mammalian genetics at Cardiff University, was awarded October 8, 2007 the Nobel Prize for medicine for his work on stem cells. Evans was honoured along with Mario Capecchi of the U.S. and fellow compatriot Oliver Smithies for the team's work on introducing genetic changes in mice using embryonic stem cells.Handout</p>

Smithies likens the knockout technique to removing a steering wheel from a car -- without it, it soon becomes clear why it has a steering wheel.

And genes linked with disease can be manipulated to create a mouse "model" of a human disease.

Capecchi said scientists knew what they wanted to do -- create genetically modified mice. But it was not easy.

Slideshow (3 Images)

"It took over 10 years just to develop the technology and now it is being used by hundreds of labs all over the world," he said.

"Embryonic stem cells were key," Dr. Jeremy Berg, director of the U.S. National Institute of General Medical Sciences, which funded some of the work, said in a telephone interview.

"When you knock out a gene in an embryonic stem cell, you can take the cells and then turn them into a mouse. There are huge benefits to being able to see the impact not just on one cell ... but on a whole organism, living and breathing."

The work has also helped speed the commercial development of drugs.

"Their demonstration of the power and the impact of this technology in the mouse highlighted the urgency of developing its use in cells of other species," said Edward Lanphier, chief executive officer Sangamo Biosciences.

But the use of human embryonic stem cells is controversial.

U.S. President George W. Bush has enforced strict limits on federal funding of the work, although it is actively encouraged in Britain.

(For the story on the Nobel medicine prize)

With additional reporting by Julie Steenhuysen in Chicago

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