Gene-Altered 'Super' Mice Are Super Athletes

But their new powers could lead to muscle damage

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HealthDay Reporter

WEDNESDAY, Aug. 25, 2004 (HealthDayNews) -- With a bit of genetic tinkering, American researchers have turned ordinary laboratory mice into high-endurance "super" athletes that handle exercise better than their rodent peers. But their newfound powers may come at a price: Higher tolerance for exercise appears to translate to quicker exhaustion down the line.

For humans -- say, Olympic athletes -- who might undergo similar treatment, there could be an even worse side effect in the brain, according to the lead author of a new study.

"It's not inconceivable that it could cause massive neural damage," said Randall S. Johnson, professor of molecular biology at the University of California at San Diego. "Maybe a gold medal is worth it, I don't know."

What is clear is that Johnson's research is giving scientists greater insight into how muscles work.

Normally, mammals burn fuel through so-called aerobic metabolism, which derives energy from oxygen. But when exertion levels rise, especially in short bursts of activity like sprints, the body switches to anaerobic metabolism, relying more on chemical processes and less on oxygen. Exhaustion eventually sets in, however, with lactic acid -- a by-product of anaerobic metabolism -- raising the risk of muscle cramps.

To test how changing the genetic makeup of mice might affect their tolerance for exercise, Johnson and his colleagues bred the animals without a gene that creates a protein known as hypoxia inducible transcription factor-1, or HIF-1. In addition to playing a role in the immune system, the protein appears to prevent the body from easily switching to anaerobic exercise.

The researchers report their findings in the Aug. 24 issue of the online journal Public Library of Science Biology.

The new "super" mice ran an average of 60 minutes on a treadmill, 10 minutes beyond the exhaustion level of normal mice. They also swam an average 45 minutes longer than the regular mice, whose endurance topped out at 150 minutes.

But while the mice could run and swim for longer periods at first, they seemed to fall apart physically in the four days after the exertion test. Their muscles became damaged and they ultimately fell behind the other mice in swimming and running tests.

This suggests that postponing the switch to a non-oxygen-based anaerobic exercise gives the mice an "initial advantage," but eventually hurts them, perhaps by letting them work past the point where they should be exhausted, Johnson said. "There's something about that exhaustion point that's telling you to stop running and stop working so hard. If you eliminate that, you damage your muscles." That damage might even spread to brain tissue, he said, although exact neurological effects remain unclear.

According to the researchers, the findings may eventually help researchers find better treatments for genetic disorders like McArdle's disease. McArdle's patients can't exercise for long because of their limited ability to generate energy through anaerobic metabolism.

And what of humans who may want to be able to exercise more? There are potential problems on that front. First, there's the risk that this type of genetic manipulation in humans would be harmful, Johnson said. Then there's the matter of who would pay for the research, which would be very expensive.

"It highly unlikely that a pharmaceutical company would go to that extent to develop a [treatment] to enhance athletic performance, unless there were some medical applications substantial enough to get the attention of the companies," said Dr. Se-Jin Lee, professor of molecular biology and genetics at Johns Hopkins University.

More information

Learn more about aerobic and anaerobic respiration from the University of Connecticut.

SOURCES: Randall Johnson, Ph.D., professor of molecular biology, University of California, San Diego; Se-Jin Lee, M.D., Ph.D., professor of molecular biology and genetics, Johns Hopkins University, Baltimore; Aug. 24, 2004, Public Library of Science Biology

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