Mice homozygous for an inactivated .alpha. 1,3-galactosyl transferase gene

A method for generating a mouse ES cell comprising at least one inactivated .alpha.-1,3 galactosyltransferase gene, the method comprising:

• (a) providing a plurality of mouse ES cells;
• (b) introducing into said cells a DNA construct comprising a disrupted mouse .alpha.-1,3 galactosyltransferase gene, wherein the disruption is by the insertion of an exogenous sequence into said gene such that the disruption prevents expression of functional .alpha.-1,3 galactosyltransferase;
• (c) incubating said cells such that homologous recombination occurs between the chromosomal sequence encoding .alpha.-1,3 galactosyltransferase and the introduced DNA construct comprising the disrupted .alpha.-1,3 galactosyltransferase gene;
• and
• (d) identifying a mouse ES cell comprising at least one inactivated .alpha.-1,3 galactosyltransferase gene.

A method for generating a mouse homozygous for an inactivated .alpha.-1,3 galactosyltransferase gene comprising:

• (a) providing a mouse ES cell comprising at least one inactivated .alpha.-1,3 galactosyltransferase gene;
• (b) inserting said cell into a mouse embryo and implanting said embryo into a female mouse;
• (c) permitting said embryo to develop into a neonatal mouse;
• (d) permitting said neonate to reach sexual maturity;
• (e) mating said sexually mature mice to obtain a mouse homozygous for said inactivated .alpha.-1,3 galactosyltransferase gene, wherein said homozygous genes results in a mouse that lacks the GAL epitope as determined by the failure of said mouse's somatic cells to bind anti-GAL antibodies and IB4 lectin, and by the increased resistance of said cells, relative to cells from a wild type mouse, to be lysed by human serum.