Tuesday, October 09, 2007

“Knockout Mountain” – Mouse Ranching UPDATED

A scientist looks at genetically modified mice that replicate human diseases. Scientists Mario Capecchi, Oliver Smithies and Martin Evans have won the Nobel Medicine prize for their work in creating "knockout mice" -- the 21st-century testbed for biomedical research. Image Credit: AFP/File/Roslan Rahman

Original Posting - March 5, 2006

Of Mice And Men - The business of raising mice for medical research is not just an enterprise where a student researcher “finds” a rare mouse with a peculiar genetic characteristic anymore. It has become “ranching” on steroids where genetic outcomes can be created and delivered through a process called Knockout!

Here is an excerpted article from AP via Yahoo News -

Mice Are Key Tool in Quest for New Drugs
By MATT CRENSON, AP National Writer Sat Mar 4, 12:39 PM ET BAR HARBOR, Maine -

When it comes to the price of mice, you pay more for defects. A mouse with arthritis runs close to $200; two pairs of epileptic mice can cost 10 times that. You want three blind mice? That'll run you about $250. And for your own custom mouse, with the genetic modification of your choosing, expect to pay as much as $100,000.
As many as 25 million mice are now used in experiments each year. Where do they come from? From the mouse industry, of course.
Yet the mouse business is a challenging one. What was once a relatively simple business of breeding and shipping animals has become an extremely challenging enterprise that requires cutting-edge technology and a mastery of difficult logistics.

"It's not just putting two animals together any more," said Terry Fisher, general manager for business development and surgical services at Charles River Laboratories, a Wilmington, Mass., which offers laboratory animals and services to pharmaceutical companies and researchers.
Mice gained their new significance not long after the completion of the human genome project in 2001. Scientists rushed to finish sequencing the mouse's DNA sequence the following year, and when they put the two genetic codes side-by-side they found something they'd always suspected — the genes of mice and humans are virtually identical. The obvious differences between us and them lie not in the genes themselves but in where, when and how those genes are activated.
Lab mice live the ultimate hothouse existence. They are kept in special rooms with filtered ventilation systems and air locks, or in cages known as "isolators" that keep them completely free of contamination from the outside world. Any technician who comes in direct contact with mice has to go through a thorough decontamination process beforehand that involves a shower and a full change of clothes. All the food, water and bedding for mice is sterilized by heating, irradiation or both.
Over decades, researchers created inbred lines of lab mice by repeatedly mating siblings to one another until every member of the strain was virtually the same genetically. That standardization made it possible for a researcher in Japan to replicate the experiment of a colleague in California without having to worry about genetic variation affecting the result.
Now researchers — and increasingly biotechnology companies — can create their own mutations, inserting or deleting genes at will.
And the award for sheer weirdness goes to Xenogen, an Alameda, Calif., outfit that can hitch the gene of interest to one that codes for the protein that makes fireflies glow. The result: Whenever and wherever the gene being studied switches on inside the mouse, it glows.
The Knockout Mouse Project would record information about the characteristics of each strain in an enormous public database that would allow researchers to link genes with their functions.
Good targets are hard to come by. But knockout mice are virtual target factories, because they are missing a single gene, and thus a single biological molecule. For example, if researchers found a knockout mouse that stayed skinny no matter how much it ate, they would immediately have a promising target for an obesity drug.
Still, it remains to be seen whether a leap can be made from mice with knocked-out genes to therapies for humans. In the past, discoveries that looked promising in rodents have often failed in human patients.

"These mice are not going to tell us everything, and sometimes they tell us nothing. But as a starting point," Austin said, "mice play a central role."

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So, if you are one of the people in our Human race that believes in the equivalence of all life on Earth … this story may disgust you. You will become, or already are, a member of PETA.

For my money, if my grandchild has a life threatening ailment, and animal research can find a cure, or ease the effect of the ailment, and thus extending her life (or anyone else who contributes to Human society for that matter) … Let’s go ranching!

UPDATE - October 9, 2007 - Excerpts from AFP via Yahoo! News -

Microscopic view of undifferentiated human embryonic stem cells are seen in this undated handout photo. Mario Capecchi, Martin Evans and Oliver Smithies won the 2007 Nobel prize for medicine or physiology for their work on stem cells, prize awarder the Karolinska Institute said on Monday. Image Credit: Handout/University of Wisconsin/Reuters

"Knockout mice" earn US-British trio Nobel Medicine prize
AFP - Mon Oct 8, 6:42 AM ET

STOCKHOLM (AFP) - Mario Capecchi and Oliver Smithies of the United States and Martin Evans of Britain won the Nobel Medicine Prize on Monday for their work in creating "knockout mice," the 21st-century testbed for biomedical research.

The trio were honoured for discovering how to genetically manipulate mouse embryonic stem cells, leading to lab rodents that replicate human disease, the Nobel jury said in its citation.

Their "ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals ... led to the creation of an immensely powerful technology," the committee said.

The discovery is technically called gene targeting but is commonly known as gene "knockout."

Engineered mice provide researchers with a lab model that is yielding insights into the fundamentals of diseases ranging from Alzheimer's to cancer and the response to new drugs, the jury said.
To date more than 10,000 mice genes -- approximately half of the genes in the mammalian genome -- have been knocked out.
The medicine prize is the first award to be announced in this year's Nobel season.
The Nobel prizes, founded by Swedish industrialist Alfred Nobel, were first awarded in 1901.

Nobel, the inventor of dynamite, died childless in 1896, dedicating his vast fortune to create "prizes to those who, during the preceding year, shall have conferred the greatest benefit on mankind."

Laureates receive a gold medal, a diploma and 10 million Swedish kronor (1.53 million dollars, 1.08 million euros) which can be split between up to three winners per prize.

The formal awarding of the prizes will take place in Stockholm on December 10.

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