Baker, J.R.; (2008) Sl00a8 in development. Doctoral thesis , University of London.

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Abstract

S100 proteins are a family of Ca2+ binding EF-hand proteins. S100A8 is a cytosolic protein expressed in myeloid cells and epithelia where it forms a stable heterodimer with another SI00 protein family member, S100A9. The S100A9 null mouse is viable and has no gross defect whereas the S100A8 null mouse is embryonic lethal. It was originally proposed that the S100A8 null mouse is lethal at E 9.0 in development due to lack of expression at E 6.5 in ectoplacental cone cells. This thesis shows that the S100A8 null phenotype is more complex than originally thought. S100A8 has a role in preimplantation development, which is previously unstudied. A small number of S100A8 null embryos survive to blastocyst but none survive implantation showing fatal compromise of S100A8 null embryos early in development. This thesis presents evidence that this lethality presents between fertilisation and E 2.5 of development. S100A8 also has a role in the murine decidua after implantation possibly key to normal murine development. S100A8 mRNA is highly expressed in maternal decidua yet S100A8 protein is not highly expressed. Foetal yolk sac cells do not express S100A8 mRNA yet they do stain positively for S100A8 protein. This thesis proposes that S100A8 protein is generated in the murine decidua and exported to the foetus where haematopoietic cells present the protein. The S100A8 protein has been shown to be expressed and stable independently of its myeloid partner, S100A9. These observations explain the discrepancy between the two SI00 null mouse phenotypes and add new insight to the S100A8 null phenotype.

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