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Molecular and Cellular Biology, April 2007, p. 3123-3130, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.01188-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Early Embryonic Lethality of Mice Lacking the Essential Protein SNEV{triangledown} ,{ddagger}

Klaus Fortschegger,1 Bettina Wagner,2,{dagger} Regina Voglauer,1 Hermann Katinger,1 Maria Sibilia,2,3 and Johannes Grillari1*

Institute of Applied Microbiology, Department of Biotechnology, University of Natural Resources and Applied Life Sciences, A-1190 Vienna, Austria,1 Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna,2 Competence Center for Biomolecular Therapeutics, A-1090 Vienna, Austria3

Received 30 June 2006/ Returned for modification 10 August 2006/ Accepted 27 January 2007

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.

* Corresponding author. Mailing address: Institute of Applied Microbiology, Muthgasse 18, A-1190 Vienna, Austria. Phone: 431360066230. Fax: 4313697615. E-mail: johannes.grillari{at}boku.ac.at

{triangledown} Published ahead of print on 5 February 2007.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} Present address: Apeiron Biologics, A-1230 Vienna, Austria.

Molecular and Cellular Biology, April 2007, p. 3123-3130, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.01188-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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