US scientists engineer 'mighty mice'
US researchers have engineered a line of "mighty mice" whose human equivalent would have similar abilities to the bicycling champion Lance Armstrong, according to research published Thursday.
"They are metabolically similar to Lance Armstrong biking up the Pyrenees; they utilize mainly fatty acids for energy and produce very little lactic acid," said Hanson, the senior author of the article which was published in the Journal of Biological Chemistry.
The genetically engineered mice can eat 60 percent more than wild mice in a control group but remain slim and fit. The "mighty mice" live longer, and some females were able to reproduce much later in life than other mice.
The researchers said some "have had offspring at 2.5 years of age, an amazing feat considering most mice do not reproduce after they are one year old."
Hanson said the strength of the mice was made possible by the fact that they produce very little lactic acid, which forms during intense exercise.
Scientists bred 500 of the mice, which also showed more aggression than other mice, over the past five years as part of a project aimed at unlocking the metabolic and physiological function of PEPCK-C in muscles and tissues.
The key to their unusual traits is the over-expression of the gene that influence production of the enzyme PEPCK-C (phosphoenolypyruvate carboxykinases), said Hanson.
The transgenic mice are descended 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," the research said.
The resulting mice showed different levels of PEPCK-C in their muscles, but one particularly active group had levels of PEPCK-C activity of nine units per gram of skeletal muscle, compared to just 0.08 units per gram in the muscles of control mice.
"From a very early age, the PEPCK-Cmus mice ran continuously in their cages," said Parvin Hakimi, a researcher in the Hanson lab.
The "mighty mice" primarily relied on "fatty acids as a source of energy during exercise, while the control animals rapidly switched from fatty acid metabolism to using muscle glycogen (carbohydrates) as a fuel; this dramatically raised the blood lactate levels," the research said.
The PEPCK-C enzyme was first discovered at the medical school of Case Western Reserve University in 1955, the study authors said.
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