SuperMouse!

"They are metabolically similar to Lance Armstrong biking up the Pyrenees."
~ Richard W. Hanson, Professor of Biochemistry at Case Western Reserve

Case Western Reserve University researchers have bred a line of abnormally strong and aggressive "mighty mice" (PEPCK-Cmus mice) that physically outperforms it's non-modified peers in every conceivable way. In fact, it can kick most human butts in several ways. The mutant mice are capable of running five to six kilometers at a speed of 20 meters per minute on a treadmill for up to six hours before stopping—a feat your average human would hard-pressed to match.

"They utilize mainly fatty acids for energy and produce very little lactic acid," said Hanson, who is the senior author of the cover article that appeared in the Journal of Biological Chemistry.

These genetically engineered mice also eat 60 percent more than their normal peers, but still remain fitter, trimmer and live and breed longer than wild mice in a control group. Some female PEPCK-Cmus mice have had offspring at 2.5 years of age, which is considered an amazing feat.  Most mice do not reproduce after they are one year old. According to Hanson, the key to this remarkable alteration in energy metabolism is the over-expression of the gene for the enzyme phosphoenolypyruvate carboxykinases (PEPCK-C).

The transgenic mice, which now number nearly 500, were derived from six founder lines that contain a chimeric gene in which a copy of the cDNA for PEPCK-C was linked to the skeletal actin gene promoter, containing the 3'-end of the bovine growth hormone gene.

It was evident from the beginning that these mice were very different from average mice. Hakimi commented, "From a very early age, the PEPCK-Cmus mice ran continuously in their cages." She said she could identify which mice were from this new line by simply watching their level of activity in their home cage. Animal behavior studies later demonstrated that the PEPCK-Cmus mice are seven times more active in their home cages than controls; in addition, the mice were also markedly more aggressive. "The enhanced level of activity noted in the PEPCK-Cmus mice extends well beyond two years of age; this is considered old-age for mice," the researchers said.

This new mouse line also has an increased content of mitochondria and high concentrations of triglycerides in their skeletal muscles, which also contributed to the increased metabolic rate and longevity of the animals.

"It is remarkable that the over-expression of a single enzyme involved in a metabolic pathway should result in such a profound alteration in the phenotype of the mouse," Hakimi and Hanson said. "Understanding the biochemical mechanisms responsible for this repatterning of energy metabolism will keep us busy for some time to come."

Posted by Rebecca Sato

Link: To view a video of the PEPCK-Cmus mouse running against the wild mouse, visit http://blog.case.edu/case-news/2007/10/26/mouse.mov .