Biol. Pharm. Bull. 28(3) 429—433 (2005)

post-translational modifications of proteins in the cell, and a UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) catalyzes the initial step in the biosynthesis of mucin-type oligosaccharide by transferring GalNAc from UDP-GalNAc to a hydroxyl amino acid on a polypeptide acceptor. This enzyme is biochemically important because it determines the number and positions of Olinked sugar chains in a protein. Recent studies on the molecular cloning of GalNAc-transferases revealed a large gene family, with 15 isozyme genes cloned to date. The large number of isozymes in the family suggests that O-glycosylation in the cell is regulated through distinctive sets of isozymes expressed in each tissue. Of the GalNAc-transferase family, GalNAc-T9, previously isolated by us, is particularly interesting in that it is specifically expressed in the brain. Although several proteins in the brain are reported to carry mucin-type carbohydrate chains, the involvement of brain-specific isozymes in vivo O-glycosylation has not been reported. Here, we report the cloning of a brain-specific putative GalNAc-transferase (pt-GalNAc-T) gene from human and rat that is most homologous to GalNAc-T9. We also found that human pt-GalNAc-T is identical to the gene, WBSCR17, located in the critical region of patients with WBS, which is characterized by a neurodevelopmental disorder caused by a haploinsufficiency of multiple genes in this region. Although WBSCR17 is most abundantly expressed in brain, with a significant amount also present in heart, the expression of its mRNA in the brain still remains to be investigated in detail. Also its gene product has not been biochemically characterized. We, therefore, examined the expression of ptGalNAc-T in the brain by conducting Northern blot and in situ hybridization analyses, and assayed the transferase activity of the recombinant pt-GalNAc-T.