CPC A01K 67/0278 (2013.01) [C07K 16/00 (2013.01); A01K 2207/15 (2013.01); A01K 2227/105 (2013.01); A01K 2267/01 (2013.01); C07K 2317/24 (2013.01)] | 19 Claims |
1. A method of making a genetically-modified rodent, the method comprising:
(a) modifying a first human chromosome to introduce a first recombination site and a second recombination site, wherein the first recombination site and the second recombination site are different, wherein the first human chromosome is human chromosome 14;
(b) modifying a first endogenous rodent chromosome to introduce a first recombination site and a second recombination site, wherein the first recombination site and the second recombination site are different;
(c) introducing the modified first human chromosome into a cell of the rodent; and
(d) inducing site specific recombination between the modified first human chromosome and the modified first endogenous chromosome, thereby replacing a sequence at the endogenous heavy chain immunoglobulin gene locus with a sequence from the modified first human chromosome,
wherein the sequence from the modified first human chromosome comprises at least human IGHV(III)-82, IGHV7-81, IGHV4-80, IGHV3-79, IGHV(II)-78-1, IGHV5-78, IGHV7-77, IGHV(III)-76-1, IGHV3-76, IGHV3-75, and IGHV(II)-74-1,
wherein the sequence from the modified first human chromosome is integrated into the endogenous chromosome by one recombination step, and the integrated sequence from the one recombination step at the endogenous heavy chain immunoglobulin gene locus is at least 500 kb,
wherein an offspring of the rodent can produce a humanized antibody.
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