| abstract |
Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises (a) a deletion in an immunoglobulin constant region C H 1 gene (optionally a deletion in a hinge region) of a heavy chain constant region gene sequence, and (b) replacement of one or all endogenous V H , D H and J H gene segments with at least one unrearranged light chain variable (V L ) gene segment and at least one unrearranged light chain joining (J L ) gene segment capable of recombining to form a rearranged light chain variable region (V L /J L ) nucleotide sequence operably linked to the heavy chain constant region gene sequence comprising a deletion in the C H 1 gene and/or insertion of a genetically engineered single rearranged light chain, wherein the mouse is capable of expressing a functional IgM, single domain antigen binding proteins, e.g., V L -single domain binding proteins, and a genetically engineered rearranged light chain. |