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 myelopoiesis 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 S100A9 mRNA between 6.5 and 8. 5 days postcoitum within fetal cells infiltrating the deciduum in the vicinity of the ectoplacental cone. Targeted disruption of the S100A8 gene caused rapid and synchronous embryo resorption by day 9. 5 of development in 100% of homozygous null embryos. Until this point there was no evidence of developmental delay in S100A8-/- embryos and decidualization was normal. The results of PCR genotyping around 7.5-8.5 days postcoitum suggest that the null embryos are infiltrated with maternal cells before overt signs of resorption. This work is the first evidence for nonredundant function of a member of the S100 gene family and implies a role in prevention of maternal rejection of the implanting embryo. The S100A8 null provides a new model for studying fetal-maternal interactions during implantation.
Passey
R J
RJ
School of Pathology, University of New South Wales, Sydney, Australia.
Williams
E
E
Lichanska
A M
AM
Wells
C
C
Hu
S
S
Geczy
C L
CL
Little
M H
MH
Hume
D A
DA
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D040501:Calgranulin A; D040502:Calgranulin B; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003656:Decidua / Q000166:cytology / Q000502:physiology; D020964:Embryo Loss / Q000235:genetics* / Q000473:pathology*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005865:Gestational Age; D007249:Inflammation / Q000235:genetics; D008431:Maternal-Fetal Exchange / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D012333:RNA, Messenger; D009418:S100 Proteins