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 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.
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107, USA.
M M
MM
Ibrahim
M
M
Razmara
D
D
Nguyen
R J
RJ
Donahue
J A
JA
Wubah
T B
TB
Knudsen
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D012336:RNA, Ribosomal, 16S / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics
D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; D016159:Tumor Suppressor Protein p53; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate