Structure of the targeted locus (not to scale). (Top) Representation of the WT unrearranged κ locus and the structure of the inserted human γHC gene replacing the Jκ region. (Middle) Resulting κ locus after targeted recombination is shown. The absence of Jκ segments precludes any Igκ LC rearrangement and expression. (Bottom) Cre-mediated deletion of the CH1 domain leads to the production of a truncated γ1HC as seen in the patient. In the absence of Cre-mediated deletion, a complete γHC is produced. Association with murine LCs is only depicted for the complete γHC (dashed boxes). The hypothetical disulfide bound between monomers of truncated γHC is also indicated (dashed line). Black triangles correspond to LoxP sites, and gray triangles are Frt sites.