Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.
Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.
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DOI：
10.1371/journal.pone.0104078
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Okano T
中科院分区：
文献类型：
--
作者：
Nakagawa K;Sawada N;Hirota Y;Uchino Y;Suhara Y;Hasegawa T;Amizuka N;Okamoto T;Tsugawa N;Kamao M;Funahashi N;Okano T
UbiA preyltransferase domain containing 1 （UBIAD1）是从人类基因组数据库中筛选和鉴定的一种新的维生素K2生物合成酶。UBIAD1最近被证明在斑马鱼和人类细胞中催化辅酶Q10 （CoQ10）的生物合成。为了研究UBIAD1在体内的功能，我们试图通过基因靶向产生缺乏人类UBIAD1同源物的小鼠。Ubiad1缺陷（Ubiad1−/−）小鼠胚胎不能存活超过胚胎7.5天，表现出小体和原肠发育停止。Ubiad1−/−胚胎干（ES）细胞不能合成维生素K2，但能够合成辅酶q9，与野生型ES细胞相似。Ubiad1 +/−小鼠发育正常，表现出正常的生长和生育能力。维生素K2组织水平和合成活性约为野生型的一半，而辅酶q9组织水平和合成活性与野生型相似。同样，由UBIAD1 +/−E15.5胚胎制备的小鼠胚胎成纤维细胞的UBIAD1表达和维生素K2合成活性约为野生型的一半，而CoQ9水平和合成活性与野生型相似。对怀孕的Ubiad1 +/−小鼠口服MK-4或CoQ10可延长其胚胎寿命至足月。这些结果表明，在小鼠中，UBIAD1负责维生素K2的合成，但可能不负责CoQ9的合成。我们认为UBIAD1通过合成维生素K2在胚胎发育中起关键作用，但可能具有维生素K2生物合成之外的其他功能。
UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1 −/−) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1 −/− embryonic stem (ES) cells failed to synthesize vitamin K2 but were able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1 +/− mice developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue levels and synthesis activity were approximately half of those in the wild-type, whereas CoQ9 tissue levels and synthesis activity were similar to those in the wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of mouse embryonic fibroblasts prepared from Ubiad1 +/− E15.5 embryos were approximately half of those in the wild-type, whereas CoQ9 levels and synthesis activity were similar to those in the wild-type. Ubiad1 −/− mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant Ubiad1 +/− mice. These results suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal role in embryonic development by synthesizing vitamin K2, but may have additional functions beyond the biosynthesis of vitamin K2.
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影响因子：
3.9
作者：
Nickerson ML;Bosley AD;Weiss JS;Kostiha BN;Hirota Y;Brandt W;Esposito D;Kinoshita S;Wessjohann L;Morham SG;Andresson T;Kruth HS;Okano T;Dean M
通讯作者：
Dean M
影响因子：
3.7
作者：
Orr A;Dubé MP;Marcadier J;Jiang H;Federico A;George S;Seamone C;Andrews D;Dubord P;Holland S;Provost S;Mongrain V;Evans S;Higgins B;Bowman S;Guernsey D;Samuels M
通讯作者：
Samuels M
影响因子：
64.8
作者：
Nakagawa, Kimie;Hirota, Yoshihisa;Okano, Toshio
通讯作者：
Okano, Toshio
影响因子：
8.7
作者：
Gaynor, PM;Zhang, WY;Kruth, HS
通讯作者：
Kruth, HS
影响因子：
5.2
作者：
Fredericks, William J.;Yin, Hankun;Malkowicz, S. Bruce
通讯作者：
Malkowicz, S. Bruce