Mol. Hum. Reprod. Advance Access originally published online on February 26, 2008
Molecular Human Reproduction 2008 14(4):207-213; doi:10.1093/molehr/gan009
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Fas-associated factor (FAF1) is required for the early cleavage-stages of mouse embryo
1Institute of Human Genetics, Faculty of Medicine, University of Göttingen, 37073 Göttingen, Germany 2Institute 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 post-translational-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
These authors contributed equally to the paper. Submitted on December 12, 2007; resubmitted on February 14, 2008; accepted on February 21, 2008.