Disruption of MSSP, c-myc single-strand binding protein, leads to embryonic lethality in some homozygous mice.
BACKGROUND
MSSP, c-myc single-strand binding protein, works as a factor for DNA replication, transcription, apoptosis induction, and myc/ras cooperative transformation. The cDNAs encoding four of the family proteins, MSSP-1, MSSP-2, Scr2 and Scr3, were cloned. These proteins possess two copies of putative RNA binding domains, RNP-A and RNP-B, and these RNA binding domains have been suggested to be indispensable to the functions of MSSP.


RESULTS
To elucidate its role in vivo, we generated Mssp knockout mice by homologous recombination in embryonic stem cells. Although intercrossing of Mssp+/- mice gave rise to mice homozygous to the mutant Mssp allele (Mssp-/-) and the Mssp-/- mice, once born, did not display an overt phenotype, the ratio of littermates born among Mssp+/+, Mssp+/- and Mssp-/- mice was 1 : 1.6 : 0.5, which is not a typical Mendelian ratio. When E2.5 embryos from the pregnant mice were cultured in vitro for 5 days, the inner cell mass and trophoblast giant cells in wild-type (Mssp+/+) E2.5 embryos developed normally. However, Mssp-/- E2.5 embryos displayed significant defects in growth and development. Since Mssp was expressed in uterine gland-transported glycogen, we evaluated the hormonal state of wild-type and Mssp-/- mice. The progesterone concentration of Mssp-/- mice was decrease to 6.5% of that of wild-type mice at E2.5.


CONCLUSIONS
These results suggest that the deletion of the mssp gene results in both the growth defect in the embryo and the hormonal defect in adult female mouse. The embryonic defect and a decreased concentration of progesterone in female mice reflect a development defect of the pre-implantation embryo in Mssp-/- mice, thereby leading to embryonic lethality.
Fujimoto
M
M
Graduate School of Pharmaceutical Sciences, College of Medical Technology, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060, Japan.
Matsumoto
K
K
Iguchi-Ariga
S M
SM
Ariga
H
H
D000818:Animals; D001755:Blastocyst; D004268:DNA-Binding Proteins / Q000235:genetics*; D020964:Embryo Loss; D051930:Endolyn; D004958:Estradiol / Q000097:blood; D005260:Female; D006720:Homozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011270:Pregnancy, Animal; D011374:Progesterone / Q000097:blood; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014599:Uterus / Q000378:metabolism
C497899:Cd164 protein, mouse; D004268:DNA-Binding Proteins; D051930:Endolyn; D014157:Transcription Factors; D011374:Progesterone; D004958:Estradiol