PSF1 is essential for early embryogenesis in mice
PSF1 is essential for early embryogenesis in mice
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DOI：
10.1128/mcb.25.23.10528-10532.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Takakura, N
中科院分区：
文献类型：
--
作者：
Ueno, M;Itoh, M;Takakura, N
Psf 1（sld five 1的伴侣）与Sld 5、Psf 2和Psf 3形成了一种新的异源四聚体复合物GINS（Go、Ichi、Nii和San;在日语中分别为5、1、2和3）。该复合物的形成对于酵母和非洲爪蟾卵提取物中DNA复制的起始是必不可少的。虽然所有的组分在高等真核生物中都很保守，但在体内的生物学功能在很大程度上是未知的。我们最初从造血干细胞cDNA文库中克隆了PSF 1的小鼠直系同源物，发现PSF 1在胚泡、成人骨髓和睾丸中表达，其中干细胞系统是活跃的。在此，我们使用基因打靶技术来确定PSF 1在体内的生理功能。PSF 1无功能突变体纯合子小鼠在着床时死于子宫内。PSFI-/-囊胚在培养中未能显示出生长，并表现出细胞增殖缺陷。我们的数据清楚地表明，PSF 1是早期胚胎发生所必需的。
Psf1 (partner of sld five 1) forms a novel heterotetramer complex, GINS (Go, Ichi, Nii, and San; five, one, two, and three, respectively, in Japanese), with Sld5, Psf2, and Psf3. The formation of this complex is essential for the initiation of DNA replication in yeast and Xenopus laevis egg extracts. Although all of the components are well conserved in higher eukaryotes, the biological function in vivo is largely unknown. We originally cloned the mouse ortholog of PSF1 from a hematopoietic stem cell cDNA library and found that PSF1 is expressed in blastocysts, adult bone marrow, and testis, in which the stem cell system is active. Here we used the gene-targeting technique to determine the physiological function of PSF1 in vivo. Mice homozygous for a nonfunctional mutant of PSF1 died in utero around the time of implantation. PSFI-/- blastocysts failed to show outgrowth in culture and exhibited a cell proliferation defect. Our data clearly indicate that PSF1 is required for early embryogenesis.