Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene.
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is the only known intracellular antioxidant enzyme that can directly reduce lipid hydroperoxide in membrane. Mitochondrial and non-mitochondrial PHGPx and sperm nuclei GPx are transcribed from one gene by alternative transcription using different first exons Ia and Ib, respectively. 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 days 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 was detected in the embryonic ectoderm and the yolk sac membrane at 7.5dpc. The results demonstrated that PHGPx is expressed in early gastrulation stage at 7.5dpc and that the expression of PHGPx was essential for normal mouse development.
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Hirotaka
H
Imai
Fumi
F
Hirao
Taro
T
Sakamoto
Kanae
K
Sekine
Yumi
Y
Mizukura
Makoto
M
Saito
Takeo
T
Kitamoto
Michiko
M
Hayasaka
Kazunori
K
Hanaoka
Yasuhito
Y
Nakagawa
D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000201:enzymology*; D047108:Embryonic Development; D005314:Embryonic and Fetal Development; D005260:Female; D018390:Gene Targeting; D005804:Genes, Lethal; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution
D012333:RNA, Messenger; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase