597481 Disclosed is a non-human mammal whose genome comprises: a plurality of human IgH V regions, one or more human D regions and one or more human J regions upstream of a host non-human mammal constant region or a plurality of human Ig light chain kappa V regions and one or more human Ig light chain kappa J regions upstream of the host non-human mammal kappa constant region and/or a plurality of human Ig light chain lambda V regions and one or more human Ig light chain lambda J regions upstream of the host non-human mammal lambda constant region wherein the non-human mammal is able to produce a repertoire of chimeric antibodies, or chimeric heavy chains wherein the non-human mammal genome into which DNA is inserted comprises endogenous V(D)J regions which have not been deleted, wherein the insertion of the human heavy chain DNA is made between the non-human mammal constant region and the last, 3, non-human mammal J region, and wherein the non-human mammal is a rodent. Further disclosed is a A non-human mammal cell whose genome comprises: a plurality of human IgH V regions, one or more human D regions and one or more human J regions upstream of a host non-human mammal constant region or a plurality of human Ig light chain kappa V regions and one or more human Ig light chain kappa J regions upstream of the host non-human mammal kappa constant region and/or a plurality of human Ig light chain lambda V regions and one or more human Ig light chain lambda J regions upstream of the host non-human mammal lambda constant region and wherein the non human mammal genome into which DNA is inserted comprises endogenous V(D)J regions which have not been deleted, wherein the insertion of the human heavy chain DNA is made between the non-human mammal constant region and the last, 3, non-human mammal J region, and wherein the non-human mammal is a rodent.
