Kauppinen R A, Halmekytö M, Alhonen L, Jänne J
Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
J Neurochem. 1992 Mar;58(3):831-6. doi: 10.1111/j.1471-4159.1992.tb09332.x.
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.
我们已经培育出一种转基因小鼠品系,其大脑中显著过表达人类鸟氨酸脱羧酶(ODC)基因。与非转基因同窝小鼠相比,转基因动物大脑中的ODC活性增加了70倍。ODC产物腐胺在转基因小鼠脑组织中的含量大于60 μmol/g,而在正常动物中,其含量低于高效液相色谱法可检测的水平。高级多胺(亚精胺和精胺)的浓度与对照值无显著差异。31P核磁共振(31P NMR)光谱分析显示,根据转基因动物大脑中核苷三磷酸α和β峰的化学位移差异计算,游离Mg2+浓度显著降低(40%)。ODC转基因小鼠大脑中较低的游离Mg2+浓度并非细胞内pH值改变或细胞高能代谢产物变化的结果。1H NMR显示,两组动物大脑中胆碱/N-乙酰天冬氨酸和总肌酸/N-乙酰天冬氨酸的比值没有差异。这些ODC转基因动物可作为体内模型,用于研究脑缺血后事件和癫痫,因为多胺被认为参与了这些过程。