Nuclear magnetic resonance spectroscopy study on energy metabolism, intracellular pH, and free Mg2+ concentration in the brain of transgenic mice overexpressing human ornithine decarboxylase gene.
We have generated a transgenic mouse line strikingly overexpressing the human ornithine decarboxylase (ODC) gene in their brain. Brain ODC activity was increased in the transgenic animals by a factor of 70 in comparison with their nontransgenic littermates. The content of brain putrescine, the product of ODC, was greater than 60 mumol/g of tissue in the transgenic mice, whereas in the normal animals it was below the level that could be detected by an HPLC method. The concentrations of the higher polyamines (spermidine and spermine) were not significantly different from control values. 31P nuclear magnetic resonance (31P NMR) spectroscopy analyses revealed a significantly reduced (40%) free Mg2+ concentration as calculated from the chemical shift differences of the nucleoside triphosphate alpha and beta peaks in the brains of the transgenic animals. The lower free Mg2+ concentration in the brains of ODC transgenic mice was not a consequence of altered intracellular pH or changes in cellular high-energy metabolites. 1H NMR showed no differences in brain choline/N-acetylaspartate and total creatine/N-acetylaspartate ratios between the two animal groups. These ODC transgenic animals may serve as models in vivo for studies on cerebral postischemic events and on epilepsy, as polyamines are supposed to be involved in these processes.
Kauppinen
R A
RA
Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
Halmekytö
M
M
Alhonen
L
L
Jänne
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics*; D009994:Osmolar Concentration
D009955:Ornithine Decarboxylase; D008274:Magnesium