A chimeric human antibody-producing mouse, wherein the antibody-producing mouse carries (1) human artificial chromosome ΔHAC or ΔΔHAC in which a 2.5 Mb region (ΔHAC) or a 1.5 Mb region (ΔΔHAC) from human chromosome 22 containing an unrearranged human antibody λ light chain locus is linked to a human chromosome 14 fragment containing an unrearranged human antibody heavy chain locus and (2) an unrearranged human antibody κ light chain transgene retained on KCo5 that is inserted into a mouse chromosome of the human antibody-producing mouse, at least both alleles of endogenous antibody heavy chain and κ light chain are disrupted or inactivated, and a human antibody heavy chain comprising a human antibody Ig γ isotype, a human antibody κ light chain, and a human antibody λ light chain are expressed in serum;
- wherein at least 85% of the cells of the human antibody-producing mouse retain the human artificial chromosome ΔHAC or ΔΔHAC.