MOLECULAR-CLONING AND CHARACTERIZATION OF LYSOSOMAL SIALIC-ACID O-ACETYLESTERASE

O-Acetylation and de-O-acetylation of sialic acids have been implicate d in the regulation of a variety of biological phenomena, including en dogenous lectin recognition, tumor antigenicity, virus binding, and co mplement activation. Applying a strategy designed to identify genes pr eferentially expressed in active sites of embryonic hematopoiesis, we isolated a novel cDNA from the pluripotent hematopoietic cell line FDC P-mixA4 whose open reading frame contained sequences homologous to pep tide fragments of a lysosomal sialic acid O-acetylesterase (Use) previ ously purified from rat liver, but with no evident similarity to endop lasmic reticulum-derived acetylesterases. The expressed Lse protein ex hibits sialic-acid O-acetylesterase activity that is not attributable to a typical serine esterase active site, Lse expression is spatially and temporally restricted during embryogenesis, and its mRNA levels co rrelate with differences in O-acetylesterase activity described in adu lt tissues and blood cell. types, Using interspecific backcross analys is, we further mapped the Ise gene to the central region of mouse chro mosome 9, This constitutes the first report on the molecular cloning o f a sialic acid specific O-acetylesterase in vertebrates and suggests novel roles for the 9-O-acetyl modification of sialic acids during the development and differentiation of mammalian organisms.