CPC C12N 15/8509 (2013.01) [A01K 67/0278 (2013.01); C07K 16/18 (2013.01); C12N 5/0696 (2013.01); C12N 15/1072 (2013.01); C12N 15/62 (2013.01); C40B 40/10 (2013.01); A01K 2207/15 (2013.01); A01K 2217/054 (2013.01); A01K 2217/072 (2013.01); A01K 2227/105 (2013.01); A01K 2267/01 (2013.01); A01K 2267/03 (2013.01); C12N 2015/8518 (2013.01); C12N 2015/8527 (2013.01)] | 7 Claims |
1. A transgenic mouse whose genome comprises an endogenous immunoglobulin heavy chain variable region locus comprising VH and JH gene segments consisting of human variable region coding sequences and mouse non-coding sequences, and a long DH (LDH) expression cassette inserted into the endogenous immunoglobulin heavy chain variable region locus to replace all endogenous DH segments, said expression cassette comprising a recombinant DH construct comprising 5-60 different human DH gene segments wherein at least two DH gene segments are directly fused and encode at least 10 amino acids of a heavy chain CDR3 (HCDR3) amino acid sequence, wherein one fused DH gene segment comprises a human DH gene segment that is mutated to remove stop codons in reading frames (RF) 1, 2 and 3, wherein the other fused DH gene segment comprises a human DH gene segment flanked by a mouse intergenic region, and wherein the mouse is functional to express said long HCDR3 amino acid sequence with a length of at least 20 amino acids in total.
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