"Marathon Mice" Spotlight a Rare Type of Muscle

Transformed muscle fibers hint at new strategies for muscle-wasting diseases

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Researchers have prompted mice to grow whole muscles from a normally rare type of muscle fiber, yielding rodents capable of running harder and for longer stretches of time than their unaltered compeers. Such animals may help to determine the role of this poorly understood type of fiber and to identify drugs capable of counteracting muscle-wasting diseases such as muscular dystrophy in people.

Muscle fibers come in two general flavors--"slow-twitch" and "fast-twitch." Slow-twitch fibers are redder (think beef or dark-meat chicken) and have more endurance than fast-twitch fibers (think pork or white meat), which contract faster but use energy less efficiently.

The muscles of the newly created mice are composed of an intermediate type of fiber that is usually present in muscles only in small amounts. The researchers inserted a hyperactive form of a mouse gene called PGC-1B into growing embryos and found that this uncommon fiber, called IIX, became abundant in the resulting mice, at the expense of fast-twitch fibers.


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These IIX-rich animals had noticeably redder, slower-twitch muscles and, as a result, were quite the little athletes, the group reports in this month's issue of the journal Cell Metabolism. They were able to run an average of 33 minutes before pooping out, compared with 26 minutes for their counterparts. "They did a lot better than their wild-type brethren," says cardiologist Zoltan Arany of Harvard Medical School, the study's lead author. "It was very impressive."

Researchers believe that PGC-1B produces a protein that helps activate other proteins, which, in turn, stimulate the genes that make IIX fibers. Members of the same group in a 2002 study discovered that a related gene, PGC-1A, turns fast-twitch fibers (called IIB) into the slow-twitch varieties (I and IIA).

Arany says the findings could help shed light on the role of this type of muscle, which, until now, had been hard to pin down, because animals normally have relatively few IIX fibers. "These mice will be a wonderful tool to study what IIX fibers are all about," he says. Earlier research indicated, for example, that muscles spend time as IIX fibers when they transform from the fast-twitch IIB to slow-twitch IIA.

Manipulating the type of fibers present in human muscle could also help treat muscle-wasting diseases such as muscular dystrophy, Arany says, because experiments have shown that slow-twitch fibers may be more resistant to wasting.

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