Muscle-bound cattle reveal meaty mutation.

In their quests to beef up, Popeye ate spinach and Arnold Schwarzenegger pumped iron. Scientists have now found that some muscle-bound cattle, such as a hulking strain prized for its tender meat, acquire their brawn more easily: They have mutations in a gene that normally curtails muscle growth.

The story of this newfound gene started with some unexpectedly muscular mice and may end, researchers speculate, with the creation of meatier cattle, chickens, and pigs--and even with treatments for muscular dystrophies.

The gene prompting such hopes encodes myostatin, one of a large family of growth-regulating proteins. While looking for new members of that family, Se-Jin Lee of the Johns Hopkins Medical Institutions in Baltimore and his colleagues unearthed myostatin and found that it is made in mouse skeletal muscle.

The scientists then created a mouse strain with a deactivated myostatin gene. The mice develop into lumbering rodents, with two to three times more skeletal muscle mass than normal. "Picture a big grizzly bear walking on all fours," says Alexandra C. McPherron, a colleague of Lee.

Lee and McPherron, as well as two other research groups, have now identified mutations in the myostatin gene of the Belgian Blue, a celebrated strain of cattle bred in Belgium over the last few decades. Fed normally, Belgian Blues develop 20 to 30 percent more muscle than average cattle, and their meat is lower in fat and unusually tender.

In the September Nature Genetics, a European team led by Michel Georges of the University of Liege in Belgium reports that the animals are missing a small portion of their myostatin gene; the group had sought a mutation in Belgian Blues for more than a decade. In the September Genome Research, Timothy P.L. Smith of the U.S. Department of Agriculture Meat Animal Research Center in Clay Center, Neb., and his colleagues in New Zealand report finding the same deletion in Belgian Blues. They also found a more subtle mutation of the gene in Piedmontese cattle, another unusually muscular strain.

Lee and McPherron's report, which includes the DNA sequence of the myostatin gene in 18 breeds of cattle, appears in the Nov. 11 Proceedings of the National Academy of Sciences.

While excessive musculature often has a downside--reduced fertility, for example--agricultural scientists still hope to beef up chickens and pigs by deactivating the myostatin gene or limiting its activity, says Lee. Moreover, since the gene remains active in adult muscles, researchers plan to explore whether inhibiting myostatin might benefit people with muscular dystrophies or the muscle-wasting often caused by cancer and AIDS.

The discovery of myostatin may even revive an old mystery. "How does an organ know its correct size?" asks Steven L. McKnight of the University of Texas Southwestern Medical Center at Dallas. In the 1960s, scientists proposed that organspecific molecules dubbed chalones regulate growth, notes McKnight. Myostatin "matches the expectations of these chalones," he says.