In vivo magnetic resonance spectroscopy of transgenic mice with altered expression of guanidinoacetate methyltransferase and creatine kinase isoenzymes

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Abstract

Mice with an under- or over-expression of enzymes catalyzing phosphoryl transfer in high-energy supplying reactions are particulary attractive for in vivo magnetic resonance spectroscopy (MRS) studies as substrates of these enzymes are visible in MR spectra. This chapter reviews results of in vivo MRS studies on transgenic mice with alterations in the expression of the enzymes creatine kinase and guanidinoacetate methyltransferase. The particular metabolic consequences of these enzyme deficiencies in skeletal muscle, brain, heart and liver are addressed. An overview is given of metabolite levels determined by in vivo MRS in skeletal muscle and brain of wild-type and transgenic mice. MRS studies on mice lacking guanidinoacetate methyltransferase have demonstrated metabolic changes comparable to those found in the deficiency of this enzyme in humans, which are (partly) reversible upon creatine feeding. Apart from being a model for a creatine deficiency syndrome, these mice are also of interest to study fundamental aspects of the biological role of creatine. MRS studies on transgenic mice lacking creatine kinase isoenzymes have contributed significantly to the view that the creatine kinase reaction together with other enzymatic steps involved in high-energy phosphate transfer builds a large metabolic energy network, which is highly versatile and can dynamically adapt to genotoxic or physiological challenges.

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Heerschap, A., Kan, H. E., Nabuurs, C. I. H. C., Klaasjan Renema, W., Isbrandt, D., & Wieringa, B. (2007). In vivo magnetic resonance spectroscopy of transgenic mice with altered expression of guanidinoacetate methyltransferase and creatine kinase isoenzymes. Subcellular Biochemistry, 46, 119–148. https://doi.org/10.1007/978-1-4020-6486-9_7

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