Geneticists rewire muscles to create a 'marathon mouse'
California geneticists have created a "marathon mouse" that can run twice as far nongenetically altered mice, and eat ravenously without growing fat.
If researchers could similarly rejigger the genetic makeup of other animal or human muscles, they might usher in an era of super race horses and ultra-athletes, and tame the obesity epidemic.
Even the researchers at the Salk Institute in California were surprised that simply changing one gene in the muscles could lead to such dramatic changes throughout the body, from the nervous system to the cardiovascular system.
"This change seems to rewire the entire system," said geneticist Ronald Evans, leader of the research team whose results appeared yesterday in a new online journal, the Public Library of Science, Biology. The results are exciting, he said, "in part because it seems some important benefits associated with exercising may be achievable without even working up a sweat."
The hundreds of mice were altered so that a protein called PPAR-delta causes their muscles to replace many of the "fast-twitch" fibers with fatigue-resistant "slow-twitch" ones. The transformed mice were able to outrun highly trained mice on a treadmill, and the marathoner was able to run more than a mile before tiring, while an ordinary mouse could manage only half that distance.
The discovery came about almost by accident, Evans said. They had expected to see a small effect from activating the PPAR-delta in skeletal muscles, but accidentally ended up with "the first animal engineered for endurance," said Evans, a member of the Howard Hughes Medical Institute. "It was a complete surprise for us; no one has ever done that before."
So far, Evans said, his team has seen few differences between the engineered and wild mice.
"They don't tend to be more active" than normal mice. They eat about the same, and there seem to be no behavioral differences -- other than being able to run twice as far, he said. But the marathon mice's muscles showed a major change in the balance between slow-twitch and fast-twitch fibers that seems to mimic the changes achieved through long-duration, vigorous exercise.
Molecular biologist Yaakov Barak, at the Jackson Laboratory in Bar Harbor, Maine, found the results "beyond anyone's imagination." But he warned that, "for all the pill-enthusiasts out there, it's highly unlikely you'll wake up to a brave new world tomorrow where you can drink your way through PPAR-delta drugs to super-manhood."
Drug companies, of course, will be trying hard to develop just such a pill. GlaxoSmithKlinehas already identified a drug that may produce similar results. A long series of trials will be needed to ensure its safety and effectiveness.
