Bulking Up, No Sweat

By choking off production of a key protein, scientists have doubled the skeletal muscle mass of lab mice--without harming vital muscles in the heart, blood vessels, and digestive system. The discovery, described in today's issue of Nature, could lead to beefier farm animals and perhaps, someday, to treatments for wasting conditions in people.

For the past 6 years, molecular biologist Se-Jin Lee and his colleagues at Johns Hopkins University have scoured the mouse genome for genes coding for undiscovered members of a family of proteins called transforming growth factors (TGF), which help control the growth of muscle, bone, and other tissues. Now Lee's group appears to have found a winner: a gene for a growth factor that appears to be switched on only in mouse embryo tissue destined to become skeletal muscle. "The pattern [of gene activity] was quite dramatic," he says. The team knocked out the gene in mice to prevent them from making the regulatory protein, dubbed myostatin. Presto, they got mighty mice, with muscles twice the size of normal littermates. The buff mice looked healthy, but Lee says they seemed "a little more sluggish and less aggressive." Gentle giants, you could say.

Although the team doesn't know where myostatin binds or exactly how it restricts muscle-cell growth, the protein is the first clear regulator of muscle development. Muscle researchers "should be very excited about this," says David Gwynne, a geneticist who heads the TGF program at Cambridge Neuroscience, in Cambridge, Massachusetts. As should breeders: Lee's team has found similar genes in chickens, pigs, and cows. And preliminary data suggest that people, too, have the gene. If so, it might be possible to develop drugs to block a human version of myostatin and spur muscle growth in, for instance, victims of muscular dystrophy or AIDS wasting syndrome.