Production of Human Antibodies from Transgenic Mice

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.