A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo

S100A8 (also known as CP10 or MRP8) was the first member of the S100 family of calcium-binding proteins shown to be chemotactic for myeloid cells. The gene is expressed together with its dimerization partner S100A9 during mye lopoiesis in the fetal liver and in adult bone marrow as well as in mature granulocytes. In this paper we show that S100A8 mRNA is expressed without S 100A9 mRNA between 6.5 and 8.5 days postcoitum within fetal cells infiltrat ing the deciduum in the vicinity of the ectoplacental cone. Targeted disrup tion of the S100A8 gene caused rapid and synchronous embryo resorption by d ay 9.5 of development in 100% of homozygous null embryos. Until this point there was no evidence of developmental delay in S100A8(-/-) embryos and dec idualization was normal. The results of PCR genotyping around 7.5-8.5 days postcoitum suggest that the null embryos are infiltrated with maternal cell s before overt signs of resorption. This work is the first evidence for non redundant function of a member of the S100 gene family and implies a role i n prevention of maternal rejection of the implanting embryo. The S100A8 nul l provides a new model for studying fetal-maternal interactions during impl antation.