Kaneda N, Sasaoka T, Kobayashi K, Kiuchi K, Nagatsu I, Kurosawa Y, Fujita K, Yokoyama M, Nomura T, Katsuki M
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Neuron. 1991 Apr;6(4):583-94. doi: 10.1016/0896-6273(91)90061-4.
Transgenic mice carrying multiple copies of the human tyrosine hydroxylase (TH) gene have been produced. The transgenes were transcribed correctly and expressed specifically in brain and adrenal gland. The level of human TH mRNA in brain was about 50-fold higher than that of endogenous mouse TH mRNA. In situ hybridization demonstrated an enormous region-specific expression of the transgene in substantia nigra and ventral tegmental area. TH immunoreactivity in these regions, though not comparable to the increment of the mRNA, was definitely increased in transgenic mice. This observation was also supported by Western blot analysis and TH activity measurements. However, catecholamine levels in transgenics were not significantly different from those in nontransgenics. These results suggest unknown regulatory mechanisms for human TH gene expression and for the catecholamine levels in transgenic mice.
已培育出携带多个拷贝人类酪氨酸羟化酶（TH）基因的转基因小鼠。转基因被正确转录，并在脑和肾上腺中特异性表达。脑中人类TH mRNA的水平比内源性小鼠TH mRNA高约50倍。原位杂交显示转基因在黑质和腹侧被盖区有大量区域特异性表达。这些区域的TH免疫反应性，虽然与mRNA的增加不可比，但在转基因小鼠中确实增加了。蛋白质免疫印迹分析和TH活性测量也支持了这一观察结果。然而，转基因小鼠中的儿茶酚胺水平与非转基因小鼠中的儿茶酚胺水平没有显著差异。这些结果表明存在未知的人类TH基因表达调控机制以及转基因小鼠中儿茶酚胺水平的调控机制。
