Sunday, August 03, 2008

"Mighty Mice" Gene Is Mutated In Beefy Bovines

The same genetic "secret formula" that gave unusually large muscles to the "mighty mice" engineered by Johns Hopkins is also at work naturally in specially bred cattle that have extra muscle, according to a new report from the researchers.

"Mutations in the myostatin gene in two different species produced the same result," says Se-Jin Lee, M.D., Ph.D., an assistant professor of molecular biology and genetics. "This strongly suggests that the normal human form of the gene, which we've already identified, helps suppress muscle growth. If we can find a drug that blocks myostatin activity, patients with muscular dystrophy or muscle wasting due to AIDS or cancer may really benefit."

Results of the study, which was supported by grants from the Edward Mallinckrodt, Jr. Foundation and MetaMorphix, Inc. are published in the Nov. 11 issue of the Proceedings of the National Academy of Science.

Cattle breeders knew nothing of myostatin when they succeeded in developing more muscular cattle breeds like the Belgian Blue and the Piedmontese. Hopkins researchers went searching for mutant forms of myostatin in these cattle after discovering what eliminating it could do to mice.

"We wondered right away if interfering with the gene in livestock could give us animals with more meat and relatively less fat," says Alexandra McPherron, Ph.D., a Hopkins postdoctoral fellow. "We first became aware that there might be some breeds of livestock that already have mutated myostatin when someone described a large-muscled breed of sheep to us."

Through literature and Internet searches, researchers learned of the Belgian Blue breed of cattle. From genetic information available online, they could see that the cattle's altered gene appeared to be in the same spot on the genetic code as human and mouse myostatin.

To confirm their suspicions, Lee and McPherron then analyzed DNA from cattle blood samples supplied by a ranch in Missouri. They also detailed the DNA blueprint of the myostatin gene from 12 non-double-muscled breeds of cattle and found that their copies of myostatin were all normal.

Scientists also sequenced the myostatin gene in humans, chickens, pigs, turkeys, sheep, baboons, zebrafish and rats, and found that there were relatively few differences among the species.

Rights to myostatin are owned by The Johns Hopkins University and exclusively licensed to MetaMorphix Inc. MetaMorphix was established in 1995 to capitalize on work by Hopkins and Genetics Institute, a private pharmaceutical company, in the field of growth and differentiation factors. Lee is a shareholder in and scientific founder of the company.

Under an agreement between MetaMorphix and The Johns Hopkins University, McPherron and Lee are entitled to shares of royalty received by the University from MetaMorphix. The University, McPherron and Lee also own MetaMorphix stock, which is subject to certain restrictions under University policy. Lee is also a consultant to MetaMorphix. The terms of this arrangement are being managed by the University in accordance with its conflict-of-interest policies.

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