Gene Tweak Makes for Mighty Mice

Nov.1, 2007 -- Scientists at Case Western Reserve University have genetically engineered mice that outrun, outlive, and out-eat ordinary mice while staying lean, light, and fertile well into old age.

Chalk it up to a change in a single gene.

That genetic tweak boosted levels of an enzyme called PEPCK-C in the mice's skeletal muscles, knocking mice's muscle metabolism into orbit.

"They are metabolically similar to Lance Armstrong biking up the Pyrenees," researcher Richard Hanson, PhD, says in a news release.

The mighty mice were seven times more active than normal mice. They showed unusually high levels of activity in their cages from the time they were 2 weeks old.

Running on special treadmills designed for mice, the genetically engineered mice left ordinary mice in the dust.

One treadmill test began at a leisurely pace. The researchers raised the treadmill's incline and speed every two minutes until the mice were exhausted and couldn't run for 10 seconds.

The genetically engineered mice ran for 32 minutes, while the ordinary mice pooped out at 19 minutes.

The genetically engineered mice ate 60% more than the ordinary mice, but they were lean and light, weighing half of what normal mice weigh with 90% less body fat.

The researchers also report that the genetically engineered mice lived longer than other mice and maintained their superior running ability.

For instance, mice that were up to 2.5 years old outran mice that were less than half their age, the study shows.

In addition, a 30-month-old genetically engineered female mouse had baby mice during the study, well past the typical mouse-bearing ages.

A major unanswered question, Hanson's team notes, is what brain changes accompany the genetically engineered mice's hyped-up activity.

Their findings appear in tomorrow's early online edition of The Journal of Biological Chemistry.