ALTERED EXPRESSION OF MITOCHONDRIAL 16S RIBOSOMAL-RNA IN P53-DEFICIENT MOUSE EMBRYOS REVEALED BY DIFFERENTIAL DISPLAY

Inactivation of the tumor suppressor p53 is associated with neural tub e 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 compare d at the head-fold stage (day 8 post coitum) using HPLC-based mRNA dif ferential display. The results of this screen revealed a deficiency of mitochondrial 16S ribosomal RNA in p53(-/-) embryos. RT-PCR showed ab normalities in 165 rRNA levels relative to some representative nuclear (COIV, beta-actin) and mitochondrial (COIII) transcripts in p53(-/-) embryos, and that 165 rRNA expression increased with development of p5 3(+/+) embryos during neurulation. Embryos that lack p53 also displaye d weakened cytochrome c oxidase staining and reduced ATP content. Duri ng neurulation, the mouse embryo switches from an anaerobic (glycolyti c) to an aerobic (oxidative) metabolism. The preliminary results of th e present study suggest that p53 may be involved, directly or indirect ly, in this transition. (C) 1998 Elsevier Science B.V. All rights rese rved.