Early Embryonic Lethality Caused by Targeted Disruption of the Mouse PHGPx Gene

摘要

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is the only known intracellular antioxidant enzyme that can directly reduce lipid hydroperoxide in membrane, To examine the role of PHGPx in development, we generated mice deficient in PHGPx by a targeted disruption of all exons of the PHGPx gene. Heterozygotes are viable, fertile, and appear normal, despite having decreased levels of three types of PHGPx mRNA and protein Embryos homozygous for PHGPx-null die between 7.5 and 8.5 post coitum (dpc), probably developing distal apoptosis. We examined the expression of PHGPx in mouse embryos using immunohistochemical analysis with anti-PHGPx mAb. The expression of PHGPx in embryogenesis was induced from 7.5 dpc and decreased to 12.5dpc. These results demonstrated that the expression of PHGPx in embryo was essential for normal mouse development.