PSF1 is essential for early embryogenesis in mice.
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.
Ueno
Masaya
M
Department of Stem Cell Biology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-0934, Japan.
Itoh
Machiko
M
Kong
Lingyu
L
Sugihara
Kazushi
K
Asano
Masahide
M
Takakura
Nobuyuki
N
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D003001:Cloning, Molecular; D020964:Embryo Loss; D047108:Embryonic Development; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D020043:Genes, Essential / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C486171:Tap1 protein, mouse