Identification and Expression in Mouse of Two Heparan Sulfate Glucosaminyl N-Deacetylase/N-Sulfotransferase Genes

Abstract

The biosynthesis of heparan sulfate/heparin is a complex process that requires the coordinate action of a number of different enzymes. In close connection with polymerization of the polysaccharide chain, the modification reactions are initiated by N-deacetylation followed by N-sulfation of N-acetylglucosamine units. These two reactions are carried out by a single protein. Proteins with such dual activities were first purified and cloned from rat liver and mouse mastocytoma. The mouse mastocytoma enzyme is encoded by an approximately 4-kilobase (kb) mRNA, whereas the rat liver transcript contains approximately 8 kb. In the present study, the primary structure of the enzyme encoded by the mouse 8-kb transcript is described. It is demonstrated that both the 4-and 8-kb transcripts have a wide tissue distribution and that they are encoded by separate genes. Characterization of the gene encoding the 4-kb transcript demonstrates that it spans a region of about 8 kb and that it contains at least 14 exons. The similarity of this gene and the previously characterized human gene for the 8-kb transcript is discussed.