Transgenic non-human mammal for producing chimeric human immunoglobulin E antibodies

A transgenic mouse, whose genome comprises an endogenous immunoglobulin heavy-chain locus comprising the replacement of its mu heavy-chain switch sequence Sμ by a human transgenic DNA construct comprising respectively from its 5′ to its 3′end, at least:

• (a) a first site-specific recombination sequence, a human immunoglobulin mu heavy-chain constant gene Cμ or a functional fragment thereof comprising at least human CH1, CH2, CH3 and CH4 exons and human membrane M1 and M2 exons, and a second site-specific recombination sequence, said first and said second recombination sequences being in the same orientation and capable of site-specific recombination, and
• (b) a human immunoglobulin epsilon heavy-chain constant gene Cε or a functional fragment thereof comprising at least human CH1, CH2, CH3 and CH4 exons and human membrane M1 and M2 exons, and
• wherein said transgenic mouse comprises endogenous B-cells which produce chimeric human immunoglobulin M (IgM) class antibodies and no endogenous IgM antibodies from said transgenic mouse, and wherein said B-cells switch chimeric human antibodies class production from immunoglobulin M to immunoglobulin E (IgE) following site-specific recombination between said first and second site-specific recombination sequences.