Transgenic mice have been created that carry human immunoglobulin heav
y and light chain genes in germline configuration and that have the co
rresponding endogenous genes silenced. The transgenes are either minig
ene constructs or large, almost authentic, transloci on yeast artifici
al chromosomes and undergo B-cell-specific DNA rearrangement and hyper
mutation in the mouse lymphoid tissue. Monoclonal antibodies with good
affinities for human antigens have been obtained after immunisation.
These mice may be a future source of human antibodies for therapy.