The invention provides a mouse whose genome comprises a transgene comprising a polynucleotide sequence comprising DNA sequences corresponding to DNA sequences from a mouse immunoglobulin locus except for polynucleotide sequences encoding one or more human immunoglobulin heavy chain variable (V) polypeptide sequences, one or more human immunoglobulin heavy chain diversity (D) polypeptide sequences, and one or more human immunoglobulin heavy chain joining (J) polypeptide sequences, wherein the polynucleotide sequences encoding the one or more human heavy chain V polypeptide sequences, the one or more human heavy chain D polypeptide sequences, and the one or more human heavy chain J polypeptide sequences replace one or more mouse immunoglobulin heavy chain V coding sequences, one or more mouse immunoglobulin heavy chain D coding sequences, and one or more mouse immunoglobulin heavy chain J coding sequences, respectively.
