Scientists create 'marathon mice'

A team of US scientists has used genetic techniques to breed mice that can run twice as far as normal mice. The animals, dubbed 'marathon' mice, have unusual stamina, and have raised more concerns over the potential use of 'gene doping' to enhance human athletic performances. The researchers, based at the Salk Institute in San Diego, published their findings in the latest issue of the open access journal PloS biology.

While normal mice can run about 900m on a treadmill before collapsing with exhaustion, the marathon mice can run up to 1,800m before stopping. The researchers created the mice by targeting a gene called PPAR-delta, which in turn affected the composition of the mouse muscle. Muscles are made up of two types of fibres, 'slow twitch' ones that are suited to endurance activities like long-distance running, and 'fast twitch' fibres capable of the rapid bursts of power required for sprinting. The two types of fibres get their energy from different sources: slow twitch fibres from fat stores, and fast-twitch from sugar. The marathon mice seem to have an increased number of slow twitch muscle fibres, and a corresponding decrease in the amount of fast twitch fibres.

The team's original aim was to switch the muscles of the altered mice so that they burned more fat, a process that uses oxygen, than sugar, which does not. Previously, they had shown that activating the PPAR-delta gene increased fat-burning in various tissues. But, said team leader Ronald Evans, 'going into this experiment, the possibility of an effect on muscle fibres was not on our radar'. It now seems that as well as controlling fat-burning, the protein made by the PPAR-delta gene can also trigger the conversion of fast twitch fibres into slow ones.

The findings have implications for work on obesity, since overweight people have fewer fat-burning slow twitch fibres that people of average weight. The researchers found that when they fed the marathon mice a high-fat diet, they didn't gain as much weight as normal mice, even without exercising. The discovery could lead to new treatments to counter obesity, or for people who have problems exercising. A drug called GW501516, which activates PPAR-delta directly, is currently being clinically tested as a treatment to lower blood cholesterol and fat, New Scientist reports. It is unclear whether or not the drug might also increase endurance in people, but Evans says: 'I suspect that animals training with the drug will increase endurance more rapidly'.