Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene
Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene
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DOI：
10.1016/s0006-291x(03)00734-4
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发表时间：
2003-05-30
影响因子：
3.1
通讯作者：
Nakagawa, Y
中科院分区：
文献类型：
--
作者：
Imai, H;Hirao, F;Nakagawa, Y
磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPx）是唯一已知的细胞内抗氧化酶，可以直接减少膜脂质过氧化氢。线粒体和非线粒体PHGPx以及精核GPx分别使用不同的第一外显子Ia和Ib通过交替转录从一个基因转录。为了研究PHGPx在发育中的作用，我们通过靶向破坏PHGPx基因的所有外显子来产生PHGPx缺陷小鼠。杂合子是可行的，可育的，并出现正常的，尽管有三种类型的PHGPx mRNA和蛋白质的水平降低。PHGPx-无效的纯合子胚胎死亡后7.5和8.5天（dpc），可能发展远端细胞凋亡。我们用抗PHGPx单克隆抗体检测了PHGPx在小鼠胚胎中的表达。7.5dpc时，在胚胎外胚层和卵黄囊膜中检测到PHGPx的表达。结果表明，PHGPx在7.5dpc的原肠胚形成早期即有表达，其表达对小鼠的正常发育是必需的。(C)2003 Elsevier Science（美国）。All rights reserved.
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 immunchistochemical analysis with anti-PHGPx mAb. The expression of PHGPx was detected in the embryonic ectoderm and the yolk sac membrane at 7.5 dpc. The results demonstrated that PHGPx is expressed in early gastrulation stage at 7.5 dpc and that the expression of PHGPx was essential for normal mouse development. (C) 2003 Elsevier Science (USA). All rights reserved.