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Mol. Hum. Reprod. Advance Access published online on February 26, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan009
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Fas-associated factor (FAF1) is required for the early cleavage-stages of mouse embryo

Ibrahim M. Adham1,5,{dagger}, Janchiv Khulan1,{dagger}, Torsten Held1, Bernhardt Schmidt2, Barbara I. Meyer3, Andreas Meinhardt4 and Wolfgang Engel1

1 Institute of Human Genetics, Faculty of Medicine, University of Göttingen, 37073 Göttingen, Germany 2 Institute of Biochemistry, Faculty of Medicine, University of Göttingen, 37073 Göttingen, Germany 3Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany 4Department of Anatomy and Cell Biology, Faculty of Medicine, University of Giessen, 35385 Giessen, Germany

5 Correspondence address. Tel: +49 551 397522; Fax: +49 551 399303; E-mail: iadham{at}gwdg.de

FAF1 was initially isolated as a Fas-associated factor and was subsequently found to interact with a subset of additional proteins that are involved in many cellular events including Fas-mediated apoptosis, heat shock signalling pathways and ubiquitin-dependent processes. Here, we describe that the 74-kDa FAF1 is ubiquitously expressed, while the expression of its posttranslational-processed 49-kDa isoform is restricted to post-meiotic male germ cells. In ovary, FAF1 protein is localized predominantly in the cytoplasm of oocytes in all follicle stages. To determine the function of FAF1 in vivo, we analysed a mouse mutant line in which a gene trap vector was inserted in the Faf1 locus. The mutation disrupts the Faf1 and leads to lethality of the Faf1GT/GT embryos near the 2-cell stage. Analysis of FAF1 expression revealed that the protein is present in early preimplantation stages, while embryonic expression of Faf1 mRNA becomes appreciable at 4-cell stage. These results indicate that the death of Faf1GT/GT at the 2-cell stage may coincide with the depletion of maternal FAF1 in these embryos. Thus, our results indicate that the FAF1 gene product is necessary for early embryonic development.

Key Words: FAF1/spermatogenesis/oogenesis/early preimplantation stages

{dagger} These authors contributed equally to the paper.

Submitted on December 12, 2007; resubmitted on February 14, 2008; accepted on February 21, 2008.


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