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Scientists Genetically Engineer Super Mice - 2001-02-01

Mr. Trouble never hangs around when he hears this mighty sound: "here I come to save the day!" That means that Mighty Mouse is on the way."

So the Mighty Mouse theme song goes.....

The cartoon character, Mighty Mouse, has amused generations of children with his antics. But children would not find a new live laboratory version nearly as colorful or exciting. Nevertheless, its physique is a significant improvement over the standard mouse. Just how much bigger are its muscles?

"Some of them are 25 percent bigger," said Nadia Rosenthal of Massachusetts General Hospital. "In general that's the average of a 25 percent increase in muscle."

The new breed of muscled, supermice created by U.S. researchers resist much of the muscle wasting that occurs during aging and several diseases. They genetically engineered the animals to be born with extra amounts of a natural hormone that promotes muscle growth.

The researchers hope to be able to put the gene for the hormone into people who need stronger muscles.

Ms. Rosenthal and several colleagues at the University of Pennsylvania created the brawny mice by transferring a gene for muscle growth into mouse embryos. As they report in the February issue of the journal Nature Genetics, the gene produced high levels of the growth hormone IGF-One to supplement the body's normal supply and the animals grew into strapping specimens.

"By doing this," she said, "we were able to show that not only does muscle become stronger, but it remains so throughout the lifespan of the animal and it is also more capable of responding to injury by regeneration later in life, which is often a problem in old muscle."

The mouse study proved to the scientists that the muscle growth hormone worked without side effects. Their ultimate goal is to transfer the gene into people whose muscles have become flaccid, either from age, diseases like AIDS and muscular dystrophy, or an accident.

"Old-fashioned exercising is always going to be your first line of defense against muscle loss," said Sharon Hesterlee, research director for the Muscular Dystrophy Association, which funded the research. "But in people who can't exercise if you suffer a fall or something happens where you are immobilized and you can't exercise as much this could be a really helpful strategy to combat that muscle loss you get from inactivity."

Ms. Hesterlee says the body produces the IGF-1 hormone to repair muscles and replace tissue, such as when bodybuilders tear down old muscle during weight lifting.

"In fact, it's so efficient that usually you get more bulk, which is why bodybuilders you see gradually bulk up," she said. "In muscular dystrophy, you get muscle damage that's too intense for the natural repair process to cope with. So what we're trying to do now is supplement this molecule IGF-1 and help boost that repair system so that you build muscle mass more quickly."

But much more animal research must be done before the gene for IGF-1 can be tested in people. In previous experiments, Nadia Rosenthal's team injected the gene into one leg of mice and that leg grew more muscular in each animal than the other legs. Now they want to see if they can transfer the gene in a way that adds bulk to all muscles at once. But as Ms. Rosenthal acknowledges, gene therapy cannot yet do this.

"In reality, we're not prepared to target the whole body because we don't know how to deliver this gene to every tissue in the body," she said. "Nobody does in the gene therapy world. Delivery is always a major stumbling block."

Ms. Rosenthal points out, however, that technologies for getting genes into many muscles at once are emerging.

"We're hoping that will speed up gene therapy in general, specifically for skeletal muscle disease," she said.