Early Embryonic Lethality of Mice Lacking the Essential Protein SNEV

Abstract

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.

SUPPLEMENTAL MATERIAL

We thank Martina Hammer, Gertraud Steniczka, Kristin Baumann, Vera Gruber, and Tanja Miehl for their excellent technical assistance.

This work was kindly supported by Polymun Scientific, Austria, and by Austrian Science Fund grant NFN093-06. B.W. was the recipient of a DOC Fellowship of the Austrian Academy of Sciences. M.S. acknowledges support by the Competence Center for Biomolecular Therapeutics, by Austrian National Bank grant ÖNB-10556, and by EC program grant QLG1-CT-2001-00869.