TARGETED INSERTION OF A VARIABLE REGION GENE INTO THE IMMUNOGLOBULIN HEAVY-CHAIN LOCUS

A mutant mouse strain has been generated in which a rearranged immunog lobulin heavy (H) chain variable (V) region gene is placed into the he avy chain locus in its natural position, replacing the J(H) elements. In homozygous mutant mice, essentially all B cells in the spleen expre ss the transgenic V(H) region in their antibodies. The proper location of the transgene relative to the constant region genes allows it to p articipate in isotype switching and undergo somatic hypermutation. Imm unoglobulin transgenic mice generated in this fashion by gene targetin g should prove useful for the exploration of immunoregulatory mechanis ms.