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5-Animals: Scientists create genetically modified 'marathon mice'



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TITLE:  Scientists create genetically modified 'marathon mice'
SOURCE: Agence France Press
DATE:   24 Aug 2004 

------------------- archive: http://www.genet-info.org/ -------------------


Tuesday August 24, 04:14 PM

WASHINGTON (AFP) - Scientists have discovered a genetic tweak that turns
mice into marathoners, but is not likely to be ready for use in humans by
for the 2008 Olympics, according to a study.

The endurance of the genetically engineered mice grew more than the
untreated mice. And the mighty mice did not become obese during periods
of inactivity and when fed high-fat diets, because the genetic change
acted like physical exercise.

"Two groups have genetically engineered different pathways that change
mice from Sunday morning joggers to Olympic marathoners," according to a
statement from the Public Library of Science Biology, an Internet
scientific magazine.

Some of the genetic modifications "not only enhance physical performance
but could presumably protect against obesity," said Ronald Evans, of Salk
Institute in San Diego, California.

"The finding that endurance and running capacity can be genetically
manipulated suggests that muscle tissue is far more adaptable than
previously thought. Maybe Olympiads can be made after all -- but don't
give up on training just yet," he said.

Evans, who headed the investigation, said that the modified mice ran
twice as fast and twice as far than their unmodified cousins, nearly
1,800 meters (1,970 yards) compared with 900 meters (985 yards). The
genetically engineered mice ran an hour longer than the normal mice.

His team succeeded in modifying the mice through a gene that is activated
only when the mouse is submitted to endurance training. Once activated,
the gene prompts an increase in physical capacity among normally idle
mice and raises their ability to burn fats, even without physical activity.

The researchers determined which muscle tissues are the fast-twitch
muscle fibers, known as type II, used for sprinting and the slow-twitch
muscles, type I, needed for endurance.

There are no known side-effects for the mice, who are nine months old.
The researchers want to know more, mostly if the genetic modification
reduces the mice's life expectancy.

There is a gap to bridge between genetic modifications possible in mice
and their application to human beings. However, Evans has already gotten
the attention of large pharmaceutical laboratories with his genetic work
in stimulating the production of so-called good cholesterol, which is
being tested in humans.

*****

Regulation of Muscle Fiber Type and Running Endurance by PPAR-d

http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/
journal.pbio.0020294
[article for reading & downloading]

Yong-Xu Wang1 , Chun-Li Zhang1 , Ruth T. Yu1 , Helen K. Cho1 , Michael C.
Nelson1 2 , Corinne R. Bayuga-Ocampo1 , Jungyeob Ham3 , Heonjoong Kang3 ,
Ronald M. Evans1 2*

1 Gene Expression Laboratory, Salk Institute, La Jolla, California,
United States of America,
2 Howard Hughes Medical Institute, La Jolla, California, United States of
America,
3 Marine Biotechnology Laboratory, School of Earth and Environmental
Sciences, Seoul National University, Seoul, Korea

Endurance exercise training can promote an adaptive muscle fiber
transformation and an increase of mitochondrial biogenesis by triggering
scripted changes in gene expression. However, no transcription factor has
yet been identified that can direct this process. We describe the
engineering of a mouse capable of continuous running of up to twice the
distance of a wild-type littermate. This was achieved by targeted
expression of an activated form of peroxisome proliferator-activated
receptor-d (PPAR-d) in skeletal muscle, which induces a switch to form
increased numbers of type I muscle fibers. Treatment of wild-type mice
with PPAR-d agonist elicits a similar type I fiber gene expression
profile in muscle. Moreover, these genetically generated fibers confer
resistance to obesity with improved metabolic profiles, even in the
absence of exercise. These results demonstrate that complex physiologic
properties such as fatigue, endurance, and running capacity can be
molecularly analyzed and manipulated.




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