Regeneron Pharmaceuticals, Inc.
Non-human animals that make single domain binding proteins

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.sub.H1 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.sub.H, D.sub.H and J.sub.H gene segments with at least one unrearranged light chain variable (V.sub.L) gene segment and at least one unrearranged light chain joining (J.sub.L) gene segment capable of recombining to form a rearranged light chain variable region (V.sub.L/J.sub.L) nucleotide sequence operably linked to the heavy chain constant region gene sequence comprising a deletion in the C.sub.H1 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.sub.L-single domain binding proteins, and a genetically engineered rearranged light chain.