The enzyme phosphoenolpyruvate carboxykinase (PEPCK), involved in gluconeogenesis, a process that involves the formation of sugars from carbohydrate precursors, such as amino acids. This function of the enzyme was well known in the liver and kidney, but in other tissues such as muscle, colon and breast, among others, much less was known of its operation. For this reason the researchers set out to design a mouse that overexpress the gene for PEPCK cytosolic (PEPCK-C) skeletal muscle to see that metabolic and physiological effects produced.
The cDNA for PEPCK-C was attached to the promoter of alpha-actin skeletal muscle, so we get the gene to be expressed in skeletal muscle.
The results were more than surprising. The transgenic mice are seven times more active than normal mice and are at twice the speed of their mouse control. A normal mouse runs 0.2 km compared with the 2 - 6 km running the genetically engineered mouse. May be at 20 meters minute for 5 or 6 hours. No cramp because half accumulate lactic acid mice unaltered.
Not only are most active, but they are much longer-lived and maintain their fertility longer. Body fat is much less in a "super mouse" and "old" than in normal young mice (WT). This despite the "super mice" eat 60% more than their controls.
Skeletal muscle also shows an increased number of mitochondria and triglyceride levels, a graphic demonstration the continued use of fatty acids by the mouse PEPCK-C during exercise.
Were there any negative effects? Yes, the PEPCK-C mice are more aggressive than wild-type mice (WT).
this work is, profound implications for several branches, including evolutionary, because it shows that overexpression of a single gene can change multiple aspects of physiology and metabolism of an animal.
The work was originally published in the Journal of Biological Chemistry.
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