Progressive loss of the spongiotrophoblast layer of Birc6/Bruce mutants results in embryonic lethality.

We have generated a mouse line with a mutant allele of the mouse Bruce/Birc6 gene induced by gene trap mutagenesis. Based on its structural features, Bruce is a member of the family of apoptosis inhibitor proteins (IAPs). This mutation leads to a truncated transcript and protein and results in a complete loss of the wildtype Bruce protein. Bruce mutant mice die from a progressive loss of their placental spongiotrophoblast layer between day 11.5 and 14.5 of embryonic development. The cause of the Bruce homozygous mutant phenotype is a lack of proliferation of spongiotrophoblast cells in the developing placenta. In contrast to in vitro data, which indicate a function for Bruce in apoptosis inhibition, the in vivo results presented here suggest instead a role for Bruce in cell division. (c) 2005 Wiley-Liss, Inc.