Peri-implantation lethality in mice lacking the PGC-1-related coactivator protein

Peri-implantation lethality in mice lacking the PGC-1-related coactivator protein
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缺乏 PGC-1 相关共激活蛋白的小鼠的植入周围致死率

DOI:
10.1002/dvdy.23769
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发表时间:
2012-05-01
影响因子:
2.5
通讯作者:
Ning, Guang
Ning, Guang
中科院分区:
生物学3区
文献类型:
--
作者:
He, Xin;Sun, Chen;Ning, Guang

文献摘要

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背景:PPAR的成员?辅激活因子-1(PGC-1)家族是调节从线粒体生物合成到氧化呼吸的细胞代谢过程的核心转录辅激活因子。PGC-1相关辅激活因子(PPRC 1或PRC)最初被鉴定为PGC-1家族的成员,被认为调节线粒体生物合成、呼吸途径和细胞增殖。然而,它的生理作用还不清楚。在这里,我们调查的生物学功能的PPRC 1在体内使用PPRC 1基因打靶产生的缺陷小鼠。结果如下:纯合缺陷PPRC 1小鼠未能形成卵柱,并在植入后但在胚胎第6.5天之前死亡,而PPRC 1杂合小鼠是可行的,可育的,与野生型同窝仔没有区别。此外,PPRC 1 mRNA在植入前的胚胎阶段表达,并在胚状体形成的第一天迅速上调。PPRC 1 mRNA随后下调,尽管其在发育的这个阶段的确切功能尚不清楚。结论:这是第一个研究表明PPRC 1在小鼠早期胚胎发育中的非冗余作用。发展动力学241:975983,2012年。(c)2012 Wiley Periodicals,Inc.
Background: Members of the PPAR? coactivator-1 (PGC-1) family are central transcriptional coactivators that regulate cell metabolic processes ranging from mitochondrial biogenesis to oxidative respiration. PGC-1-related coactivator (PPRC1 or PRC), initially identified as a member of the PGC-1 family, is believed to regulate mitochondria biogenesis, respiration pathways, and cell proliferation. However, its physiological role is not clearly understood. Here, we investigate the biological functions of PPRC1 in vivo using PPRC1 deficient mice generated by gene targeting. Results: Homozygous deficient PPRC1 mice failed to form egg cylinders and died after implantation but before embryonic day 6.5, whereas mice heterozygous for PPRC1 were viable, fertile and indistinguishable from their wild-type littermates. Furthermore, PPRC1 mRNA was expressed at the embryonic stage before implantation and was rapidly up-regulated during the first day of embryoid body formation. The PPRC1 mRNA was then subsequently down-regulated, although its precise function at this stage of development was unclear. Conclusions: This is the first study to suggest a nonredundant role for PPRC1 in mouse early embryonic development. Developmental Dynamics 241:975983, 2012. (c) 2012 Wiley Periodicals, Inc.