Ibrahim M M, Razmara M, Nguyen D, Donahue R J, Wubah J A, Knudsen T B
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USA.
Biochim Biophys Acta. 1998 Jul 24;1403(3):254-64. doi: 10.1016/s0167-4889(98)00066-4.
Inactivation of the tumor suppressor p53 is associated with neural tube defects and altered teratogenicity in early embryos. To gain insight into the function of p53 during early embryogenesis, RNA profiles of wild-type p53(+/+) and p53(-/-) null mutant mouse embryos were compared at the head-fold stage (day 8 post coitum) using HPLC-based mRNA differential display. The results of this screen revealed a deficiency of mitochondrial 16S ribosomal RNA in p53(-/-) embryos. RT-PCR showed abnormalities in 16S rRNA levels relative to some representative nuclear (COIV, beta-actin) and mitochondrial (COIII) transcripts in p53(-/-) embryos, and that 16S rRNA expression increased with development of p53(+/+) embryos during neurulation. Embryos that lack p53 also displayed weakened cytochrome c oxidase staining and reduced ATP content. During neurulation, the mouse embryo switches from an anaerobic (glycolytic) to an aerobic (oxidative) metabolism. The preliminary results of the present study suggest that p53 may be involved, directly or indirectly, in this transition.
肿瘤抑制因子p53的失活与神经管缺陷以及早期胚胎致畸性改变有关。为深入了解p53在早期胚胎发育过程中的功能，利用基于高效液相色谱的mRNA差异显示技术，在头褶期（交配后第8天）比较了野生型p53(+/+)和p53(-/-)基因敲除突变小鼠胚胎的RNA谱。该筛选结果显示p53(-/-)胚胎中线粒体16S核糖体RNA缺乏。逆转录聚合酶链反应表明，相对于p53(-/-)胚胎中一些代表性的核转录本（细胞色素c氧化酶亚基IV、β-肌动蛋白）和线粒体转录本（细胞色素c氧化酶亚基III），16S rRNA水平存在异常，并且在神经胚形成过程中，随着p53(+/+)胚胎的发育，16S rRNA表达增加。缺乏p53的胚胎还表现出细胞色素c氧化酶染色减弱和ATP含量降低。在神经胚形成过程中，小鼠胚胎从无氧（糖酵解）代谢转变为有氧（氧化）代谢。本研究的初步结果表明，p53可能直接或间接参与了这一转变。
