Disclosed is a human antibody producing mouse, which carries: (a) an unrearranged human antibody heavy chain gene locus, (b) an unrearranged human antibody .kappa. light chain gene locus and (c) an unrearranged human antibody .lambda. light chain gene locus, wherein at least one of (a), (b) and (c) is retained on one or more human derived chromosome fragments and at least one of (a), (b) and (c) is inserted into a mouse chromosome, and further wherein at least both alleles of endogenous heavy chains and both alleles of endogenous .kappa. light chains are inactivated, and the mouse expresses human antibody heavy chain, human antibody .kappa. light chain and human antibody .lambda. light chain in serum of the mouse. The mouse is useful in producing human antibodies.
