Transgenic non-human animals for producing heterologous antibodies

A transgenic mouse containing in its genome a transgene comprising in operable linkage a plurality of human V genes, a plurality of human D genes, a plurality of human J genes, a human .mu. C.sub.H gene, at least two different non-.mu. human C.sub.H genes and associated isotype switching sequences, wherein human .mu. and human .gamma. switch sequences are located in closer proximity to each other than in the naturally occurring human immunoglobulin locus;

• and wherein in lymphocytes of said mouse the transgene undergoes productive VDJ rearrangement and .mu. to .gamma. isotype switching by recombination between the human .mu. and human .gamma. switch sequences such that the mouse produces a serum containing immunoglobulins of at least three human heavy chain isotypes in response to antigenic stimulation.