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

Researchers create "mighty mouse" with gene tweak that doubles muscle strength
Pumped-up muscle tissue (in blue) in a high performing "mighty mouse"
Pumped-up muscle tissue (in blue) in a high performing "mighty mouse"
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Pumped-up muscle tissue (in blue) in a high performing "mighty mouse"
Pumped-up muscle tissue (in blue) in a high performing "mighty mouse"
A rendering of the protein structure of NCOR1
A rendering of the protein structure of NCOR1
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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.

A rendering of the protein structure of NCOR1
A rendering of the protein structure of NCOR1

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.

Better muscles thanks to a genetic knock-out

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Racqia Dvorak
Forget Mighty Mouse, I\'m thinking Captain America.
Dread Zontar
Mighty Mouse be damned; we want Universal Soldier!
Jay Barone
I could easily see a large amount of people being born with genetic engineered advantages like this in the future. And more and more people coming on board so that they and their children will not be left behind.
Ron Paul 2012!
Bob Ehresman
Too ready for the \"no rules\" olympics.... :-)
John Buttimer
Well, this opens up a new realm for us to live on other planets, and even lets us live in space longer.
Nick Ward
John makes a great point here. With study pointing to the detriment of muscle in null gravity situations, this might be a way to combat the long-term effects of planetary orbit or extended space travel. Now if they could unlock the key to bone growth then this little hypothesis might be a step closer to completion.
Regeneron Pharmaceuticals (NY USA) made these 10 years ago! They have made other types as well, including mice with fully human immune systems!
When does Terminator production begin?
Mr Stiffy
And the trade offs are?
Most people age and get decrepit totally from the lack of activity and the lack of hard exercise, and not unexpectedly - from eating junk foods.
Look up Youtube exercise aging raw food gym etc.. and there are people in their 70\'s and 80\'s and way beyond who are in brilliant condition.
David Leithauser
My questions is, what is the benefit of this gene that they are suppressing? There must be some evolutionary benefit to the gene, or it would not be part of our DNA. Perhaps it causes fat production instead of muscle production, since fat might actually be more useful than muscle in a primitive environment where the food supply is irregular. Of course, that environment does not exist any more in the developed world, so the gene is essentially obsolete here. Still, while I love the idea of genetically engineering a race of super people, it is important to know exactly what you are giving up when you start messing with genes.
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