Various lines of PEPCK-Cmus mice expressed PEPCK-C at different levels, but one very active line of PEPCK-Cmus mice had levels of PEPCK-C activity of 9 units/gram skeletal muscle, compared to only 0.08 units/gram in the muscles of control animals. The skeletal actin gene promoter directs expression of PEPCK-C exclusively to skeletal muscle. 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. Parvin Hakimi, the article’s lead author and a researcher in the Hanson lab, developed this new line of PEKCK-C mice over the past five years as part of on-going research aimed at understanding the metabolic and physiological function of PEPCK-C in skeletal muscle and adipose tissue. 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). Some female PEPCK-Cmus mice have had offspring at 2.5 years of age, an amazing feat considering most mice do not reproduce after they are one year old. These genetically engineered mice also eat 60 percent more than controls, but remain fitter, trimmer and live and breed longer than wild mice in a control group. Hanson, the Leonard and Jean Skeggs Professor of Biochemistry at Case Western Reserve and the senior author of the cover article that appeared in the Journal of Biological Chemistry, entitled “Over Expression of the Cytosolic Form of Phosphoenolpyruvate Carboxykinase (GTP) in Skeletal Muscle Repatterns Energy Metabolism in the Mouse.” “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 Richard W.
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