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Production of Human Antibodies from Transgenic Mice

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Mice transgenic for human immunoglobulin genes offer the opportunity to investigators to derive fully human antibodies using well-established hybridoma technology. Several different strains of such mice are available, and can be obtained under certain conditions from various commercial entities (1 3 ). The brand names of these mice include XenoMouse�, HuMAb� Mouse, TC™ mouse, and KM™ mouse. The leading transgenic mice all share certain properties. These include the following:
1. 
the endogenous murine heavy-chain locus has been inactivated by knocking out either all of the JH genes or the Cμ gene (4 );
2. 
the endogenous murine kappa light-chain locus has been inactivated by knocking out the Jκ and/or the Cκ genes;
3. 
the endogenous murine lambda light-chain locus remains intact and functional;
4. 
the human heavy-chain transgene contains, at minimum, the majority of the human VH genes, all the D genes, all the JH genes, Cμ Cδ , and at least one Cγ gene, together with regulatory elements; and
5. 
the human kappa light-chain transgene contains the majority of the human Vκ genes, all the Jκ genes, and the Cκ gene, together with regulatory elements.
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