Early embryonic lethality of mice lacking the essential protein SNEV.
SNEV (Prp19, Pso4, NMP200) is a nuclear matrix protein known to be involved in pre-mRNA splicing, ubiquitylation, and DNA repair. In human umbilical vein endothelial cells, SNEV overexpression delayed the onset of replicative senescence. Here we analyzed the function of the mouse SNEV gene in vivo by employing homologous recombination in mice and conclude that SNEV is indispensable for early mouse development. Mutant preimplantation embryos initiated blastocyst formation but died shortly thereafter. Outgrowth of SNEV-null blastocysts showed a lack of proliferation of cells of the inner cell mass, which subsequently underwent cell death. While SNEV-heterozygous mice showed no overt phenotype, heterozygous mouse embryonic fibroblast cell lines with reduced SNEV levels displayed a decreased proliferative potential in vitro. Our experiments demonstrate that the SNEV protein is essential, functionally nonredundant, and indispensable for mouse development.
Fortschegger
Klaus
K
Institute of Applied Microbiology, Muthgasse 18, A-1190 Vienna, Austria.
Wagner
Bettina
B
Voglauer
Regina
R
Katinger
Hermann
H
Sibilia
Maria
M
Grillari
Johannes
J
D000818:Animals; D001755:Blastocyst / Q000166:cytology; D049109:Cell Proliferation; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000473:pathology*; D005260:Female; D005313:Fetal Death; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D034521:Nuclear Matrix-Associated Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein
D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; C518638:Prpf19 protein, mouse; D000072260:RNA Splicing Factors; D012333:RNA, Messenger