Generation of a Mouse Strain That Produces Immunoglobulin ``kappa'' Chains with Human Constant Regions

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Humanized antibodies are highly efficient as immunotherapeutic reagents and have many advantages over rodent antibodies.A mouse strain was generated by gene targeting to replace the mouse ``kappa'' light chain constant (C) region gene with the human C sub ``kappa'' gene. Mice homozygous for the replacement mutation (C sub ``kappa'' R) produced normal concentrations of serum antibodies, most of which carry chimeric ``kappa'' light chains, and mounted normal immune responses to hapten-protein conjugates. This technology provides a feasible option for the generation of high-affinity humanized antibodies by means of the powerful somatic hypermutation-selection mechanism.

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