It can run for hours at 20 metres per minute without getting tired. It
lives longer, has more sex, and eats more without gaining weight. Could
the science that created this supermouse be applied to humans?
By Steve Connor, Science Editor
Scientists have been astounded by the creation of a genetically
modified "supermouse" with extraordinary physical abilities –
comparable to the performance of the very best athletes – raising the
prospect that the discovery may one day be used to transform people's
capacities.
The mouse can run up to six kilometres (3.7 miles) at a speed of 20
metres per minute for five hours or more without stopping. Scientists
said that this was equivalent of a man cycling at speed up an Alpine
mountain without a break. Although it eats up to 60 per cent more food
than an ordinary mouse, the modified mouse does not put on weight. It
also lives longer and enjoys an active sex life well into old age –
being capable of breeding at three times the normal maximum age.
American scientists who created the mice – they now have a breeding
colony of 500 – said that they were stunned by their abilities,
especially given that the animals came about as a result of a standard
genetic modification to a single metabolism gene shared with humans.
They emphasised that the aim of the research was not to prepare the way
to enhance the genes of people. However, they accepted that it may be
possible to use the findings to develop new drugs or treatments that
could one day be used to "enhance" the natural abilities of athletes.
The professor of biochemistry at Case Western Reserve University at
Cleveland in Ohio, Richard Hanson, said that the physical performance
of the supermouse can only be compared to supremely fit athletes like
the cyclist Lance Armstrong, who won the Tour de France seven
consecutive times from 1999 to 2005. The genetic alteration to a gene
involved in glucose metabolism appears to stimulate the efficient use
of body fat for energy production. At the same time, the mice do not
suffer from a build up of lactic acid – which causes muscle cramps – a
feature also seen in the best endurance athletes.
Professor Hanson said yesterday: "They are metabolically similar to
Lance Armstrong biking up the Pyrenees. They utilise mainly fatty acids
for energy and produce very little lactic acid. They are not eating or
drinking and yet they can run for four or five hours. They are 10 times
more active than ordinary mice in their home cage. They also live
longer – up to three years of age – and are reproductively active for
almost three years. In short, they are remarkable animals.
"On the downside, they eat twice as much as control mice, but they are
half the weight, and are very aggressive. Why this is the case, we are
not really sure."
Professor Hanson, who led the 15-strong team of researchers, said that
the first supermouse was created about four years ago by injecting a
highly active form of a gene for an enzyme called phosphonenolpyruvate
carboxykinase (PEPCK-C) into a mouse embryo. The results of studies on
the mice are published for the first time today in the Journal of
Biological Chemistry.
Professor Hanson said: "We humans have exactly the same gene. But this
is not something that you'd do to a human. It's completely wrong. We do
not think that this mouse model is an appropriate model for human gene
therapy. It is currently not possible to introduce genes into the
skeletal muscles of humans and it would not be ethical to even try."
However, it may be possible for pharmaceutical companies to use the
findings to develop new drugs that enhance muscle performance, which
may benefit certain patients. Professor Hanson accepted that it was
possible athletes might misuse any future drug developed in this way.
He said: "It's very possible. It's a different approach to putting a
gene into a human. I would only do that to help anyone who suffers from
disorders such as cystic fibrosis."
The aim of the research was to gain a greater understanding of the
PEPCK-C enzyme, which is present mainly in the liver and kidneys. As a
result of the genetic modification, the mighty mice have up to 100
times the concentration of the enzyme in its muscles compared with
ordinary mice.
Professor Hanson said: "The purpose of our experiment was to study
energy metabolism in the mice and the role that a single, metabolically
important enzyme might play in a tissue in which it is not normally
expressed at high levels."
He said that the physical and behavioural changes in the modified mice
were completely unexpected. Usually, scientists have to carry out blood
tests to see if there has been any effect of altering the genes, but
these mice were noticeably different at a very early age.
He said: "We could spot them at just a few weeks after birth. They
popped around the cage like popcorn. We found that they were about 10
times as active as ordinary mice."
Further research on the mice could shed light on the link between
high-calorie diets and cancer, and low-calorie diets and longevity. He
said: "Our animals live longer and eat almost twice as much as ordinary
mice – this is a model to study."
Original
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