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Abstract

Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the .alpha. 1.fwdarw.3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding .alpha. 1.fwdarw.3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of .alpha. 1.fwdarw.3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of .fwdarw.1.fwdarw.3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation.

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First Claim