DECIPHERING SIALIC ACID O-ACETYLATION

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The aim of this proposal is to investigate the impact of sialic acid O-acetylation on kidney development and function by using novel genetic mouse models. O-Acetylation significantly contributes to the structural diversity of sialoglycans, but its function in vivo remains poorly understood. In preliminary work, we demonstrated that genetic ablation of the murine sialate O-acetyltransferase CASD1 results in a complete loss of 9-O- and 7,9-O-acetylated sialoglycans and causes a renal tubular phenotype. To understand how sialic acid O-acetylation contributes to kidney integrity, we will perform functional assays on isolated primary cells and explore the contribution of O-acetylated sialoglycans on tubular epithelial and vascular endothelial cells through the generation of cell type-specific Casd1 knockout mice. By functional assessment of rare, patient-derived CASD1 variants, we will investigate whether CASD1 is a novel candidate gene for human kidney disease. Within the research unit, our project is closely linked to projects 2, 5 and 9, and will benefit from specific interactions with projects 1, 6, and 8.