PDF(Pubmed)
Abstract：
The enzyme dUTPase has an essential role in maintaining genomic integrity. In mouse, nuclear and mitochondrial isoforms of the enzyme have been described. Here we present the isoform-specific mRNA expression levels in different murine organs during development using RT-qPCR. In this study, we analyzed organs of 14.5-day embryos and of postnatal 2-, 4-, 10-week- and 13-month-old mice. We demonstrate organ-, sex- and developmental stage-specific differences in the mRNA expression levels of both isoforms. We found high mRNA expression level of the nuclear isoform in the embryo brain, and the expression level remained relatively high in the adult brain as well. This was surprising, since dUTPase is known to play an important role in proliferating cells, and mass production of neural cells is completed by adulthood. Thus, we investigated the pattern of the dUTPase protein expression specifically in the adult brain with immunostaining and found that dUTPase is present in the germinative zones, the subventricular and the subgranular zones, where neurogenesis occurs and in the rostral migratory stream where neuroblasts migrate to the olfactory bulb. These novel findings suggest that dUTPase may have a role in cell differentiation and indicate that accurate dTTP biosynthesis can be vital, especially in neurogenesis.
摘要：
dUTPase酶在维持基因组完整性方面具有重要作用。在老鼠身上,已经描述了该酶的核和线粒体同工型。在这里，我们介绍了使用RT-qPCR在发育过程中不同鼠器官中的同工型特异性mRNA表达水平。在这项研究中,我们分析了14.5天胚胎和出生后2-的器官，4-,10周龄和13月龄小鼠。我们展示器官-，两种同工型mRNA表达水平的性别和发育阶段特异性差异。我们发现胚胎大脑中核同工型的mRNA表达水平很高，并且在成人大脑中的表达水平也保持相对较高。这令人惊讶，由于已知dUTPase在细胞增殖中起重要作用，神经细胞的大规模生产在成年期完成。因此，我们用免疫染色研究了成人大脑中dUTPase蛋白表达的模式，发现dUTPase存在于发芽区，脑室下和颗粒下区域,发生神经发生的地方，以及成神经细胞迁移到嗅球的前端迁移流中。这些新发现表明dUTPase可能在细胞分化中起作用，并表明准确的dTTP生物合成可能是至关重要的。尤其是在神经发生方面。
