Targeted insertion of a variable region gene into the immunoglobulin heavy chain locus.

A mutant mouse strain has been generated in which a rearranged immunoglobulin heavy (H) chain variable (V) region gene is placed into the heavy chain locus in its natural position, replacing the JH elements. In homozygous mutant mice, essentially all B cells in the spleen express the transgenic VH region in their antibodies. The proper location of the transgene relative to the constant region genes allows it to participate in isotype switching and undergo somatic hypermutation. Immunoglobulin transgenic mice generated in this fashion by gene targeting should prove useful for the exploration of immunoregulatory mechanisms.