Xenotransplantation is one of the most attractive solutions for the current worldwide shortage of organs. The knocking out of alpha 1,3-galactosyltransferase in pigs resulted in a drastic reduction in xenoantigenicity. However, more recent Studies indicate that other xenoantiaens. so-called non-Gal antigens. will also need to be downregulated. fit this study, pig N-acetylglucosaminlyltransferase I (GnT-I), a key enzyme that initiates the biosynthesis of hybrid- and complex-type N-linked sugar chains, was isolated and the pigGnT-I.2 specific for the O-linked sugar chain was also isolated. Point Mutants, pigGnT-I(1123) and pigGnT-I(320), were subsequently constructed. While pigGnT-I(123) shows an indistinct dominant negative effect for endogenous GnT-I in pig cells, pigGnT-I(320) had a drastic effect. In addition, in the case of pig cell transfectants with pigGnT-I(320). cell surface carbohydrate Structures were significantly altered and its antigenicity to human serum was reduced. Consequently, pigGnT-I(320) appears to be potentially useful in xenotransplantation by remodeling the carbohydrate structures on pig cells. (c) 2006 Elsevier Inc. All rights reserved.