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Molecular and Cellular Biology, December 2005, p. 10528-10532, Vol. 25, No. 23
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.23.10528-10532.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

PSF1 Is Essential for Early Embryogenesis in Mice

Department of Stem Cell Biology, Cancer Research Institute, Kanazawa University,¹ Institute for Experimental Animals, Kanazawa University Advanced Science Research Center, Kanazawa, Japan,² PRESTO, Japan Science Technology Agency, Saitama, Japan³

Received 17 May 2005/ Returned for modification 9 August 2005/ Accepted 14 September 2005

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. PSF1^–/– blastocysts failed to show outgrowth in culture and exhibited a cell proliferation defect. Our data clearly indicate that PSF1 is required for early embryogenesis.

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