Researchers create "mighty mouse" with gene tweak that doubles muscle strength

He can't fly just yet, but a team of scientists have made a big step towards creating a real-life Mighty Mouse. Researchers at the Salk Institute for Biological Studies, along with two Swiss institutions, Ecole Polytechnique Federale de Lausanne (EPFL) and the University of Lausanne, created a batch of super-strong mice and worms by tweaking a gene that normally inhibits muscle growth.

The scientists acted on a genome regulator - known as NCOR1 - and were able to change the activity of certain genes. In simpler English, the scientists shut off the thyroid hormone that keeps most mammals from turning into the Incredible Hulk. The result was a strain of mice with muscles that were twice as strong as normal.

Besides nearly bringing the world's second most popular cartoon mouse to life (Mickey comes in at number one) and making the premise of the film Tremors seem slightly more feasible, the findings could help in the creation of new treatments for muscle degeneration.

"This could be used to combat muscle weakness in the elderly, which leads to falls and contributes to hospitalizations," Johan Auwerx, the lead author from EPFL says. "In addition, we think that this could be used as a basis for developing a treatment for genetic muscular dystrophy."

Gain without the pain

The research could also yield more good news for the epidemic of obesity that plagues many western countries. "There are now ways to develop drugs for people who are unable to exercise due to obesity or other health complications, such as diabetes, immobility and frailty," says Ronald M. Evans, who led the Salk team. "We can now engineer specific gene networks in muscle to give the benefits of exercise to sedentary mice."

Auwerx describes molecules such as NCOR1 as "molecular brakes" that slow down the activity in genes. Releasing these brakes through gene manipulation increases that activity level, providing more energy to build muscle.

The benefits of releasing those molecular brakes don't stop at increased muscle strength. The stronger mice also saw improved endurance, and were capable of running both faster and longer before tiring, covering twice the distance of normal mice in experiments. Researchers say the mutated mice were also more tolerant to cold.

Going after the genetic inhibitor is the inverse of previous approaches that involved "genetic accelerators." Researchers believe that because the method proved successful in both mice and worms, then the same techniques could be applied to a wide range of species.

Potential for drugs and cheating in sport?

The scientists say they have not seen any harmful side effects from zapping NCOR1 in muscles, and are beginning to investigate the potential for drugs that could serve the same function.While the results have not yet been confirmed in humans, they're likely to spark a lot of interest among athletes who wouldn't mind a quick short cut to doubling their strength and endurance. As it stands right now, however, so-called "gene doping," which includes the use of genetically-modified cells, is banned by the World Anti-Doping Agency.

The research team's findings appear in the journal Cell.

EPFL's Auwerx provides a summary of the research in the following video.