Mudge

Johns Hopkins researchers have genetically engineered mice to grow herculean muscles, an achievement that eventually may lead to the development of treatments for muscular dystrophy and other muscle-wasting diseases.

"The first thing that we noticed was that the knockout mice had unusually large shoulders and hips," says Alexandra McPherron, a Hopkins Ph.D. student and first author of a paper in this week's Nature. "On closer analysis we found that all their muscles were two to three times normal size."

To create the mice, scientists "knocked out" a newly discovered gene called growth/differentiation factor 8 (GDF 8), erasing it from the rodents' genetic code. Without GDF 8, which limits skeletal muscle growth, the mice's muscles grew dramatically.

Hopkins researchers already have identified the human form of GDF 8 and are investigating whether it performs the same function in humans.

So far, the gene appears to be active only in skeletal muscle tissue, which may be why removing it seems to have had little effect beyond enlarging the mice's muscles.

"Except for the muscles, the mice appear to be normal and healthy," says McPherron.

Rights to GDF 8, first identified in mice by a research team led by Se-Jin Lee, M.D., Ph.D., an assistant professor of molecular biology and genetics, are owned by Johns Hopkins University and exclusively licensed to MetaMorphix Inc., a company that funded the knockout mice study.

"We're excited that GDF 8 could give us new opportunities to treat the many muscle-wasting diseases like muscular dystrophy or cachexia, the muscle loss that accompanies some cancers and AIDS," says Lee.

"We've also found GDF 8 in cows and chickens, so we might be able to interfere with it to create livestock with more meat and relatively less fat," says Lee.

Lee's group found the gene by searching for new members of the transforming growth factor-beta (TGF-beta) gene family.

Other TGF-beta genes include bone morphogenetic proteins, a group of genes that helps stimulate bone growth, and glial-derived neurotrophic factor, a gene that sustains nerve cells. Proteins from both of these groups are already in clinical trials for treatment of various disorders.

Hopkins researchers altered the GDF 8 gene in mouse embryonic stem cells, which appear very early in a mouse's development before cell specialization occurs. When these cells went on to produce egg or sperm cells in a mouse, the genetic changes Lee made were passed on to every cell of the mouse's descendants when they reproduced. Nearly a year after their initial creation, the mutant mice show no other signs of abnormality and can reproduce healthy offspring.

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.

Kinesiology Comp Bench
MaxCalc Motivation Bench form Charles Poliquin
When I let go of what I am, I become what I might be. Lao-Tzu

gr81

I want some

crackerjack414

could run into a few problems in the body builder community unlimmited muscle growth. Can any one imagine how that would change the phsyques. Id like to see how these mice's muscles mature.

Mudge

Connective tissue is one thought.

Kinesiology Comp Bench
MaxCalc Motivation Bench form Charles Poliquin
When I let go of what I am, I become what I might be. Lao-Tzu