Case Western develops superstrong mice

Altering genes and enzymes in mice results in super athletes, the Lance Armstrongs of the rodent world.

Ohio's Case Western Reserve University has some mice that will kick your butt.

Credit: Case Western Reserve University
Parvin Hakimi (left) and Richard Hanson
(right). She bred the mice and he
studies enzymes.

Researchers at the university have bred a strain of "mighty mice," known as PEPCK-Cmus mice because of specific genetic enhancements, that can run for six hours at a speed of 20 meters per minute, or a total of 5 or 6 kilometers.

The mice also eat 60 percent more than standard mice, but remain fit and trim and are actually smaller. One female gave birth to offspring at two years and 11 months, far later than mice in the wild, which typically stop giving birth after one year. The mighty mice also live longer.

"My technician could open the cage and pick them out by their activity at two weeks of age," said Richard Hanson, Leonard and Jean Skeggs professor of biochemistry at Case Western Reserve. "Our animals mirror the kind of (metabolic) activity you see in Lance Armstrong. They have an ability to utilize fatty acid for long periods of time and not have lactic acid build-up."

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Video: The mighty mice
Case Western scientists altered the genetic code of mice artificially to induce the production of a specific enzyme in muscle tissue.

The results were both unexpected and remarkable, Hanson added. Potentially, the research could help enhance cancer treatment in humans or allow us to better understand the human metabolic process. It also could even change some of the current thinking on dietary recommendations for sick patients. Maybe it isn't the calories you eat, but what you do with them, Hanson speculated.

But a great deal of study and research lies ahead and any conclusion is premature, he said.

An article by Hanson and Parvin Hakimi, a researcher in Hanson's lab who developed the mice, appeared in the Journal of Biological Chemistry.

The key to the superperformance isn't the drug EPO. Instead, it is a gene that produces the enzyme phosphoenolpyruvate carboxykinase (PEPCK-C) in muscle tissue. The enzyme is ordinarily used to metabolize glucose in the liver, Hanson said. However, minute amounts of it are naturally found in muscle tissue.

Hakimi came up with a way to alter the genetic code in the experimental mice that overproduces the enzyme. One line of the supermice had levels of PEPCK-C at 9 units per gram of skeletal muscle. Ordinarily, a mouse might produce 0.08 units per gram. Case Western has produced about 500 of these transgenic mice, and this genetic combination would not occur in the wild. "We tested what the metabolic function is in muscle tissue," Hanson said.

The questions for future research include what effect elevated levels of PEPCK-C would have in humans.

 

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