FIELD: biotechnology.
SUBSTANCE: described is a method of producing a variable region of a λ human light chain, the method comprising: (a) immunising a genetically modified mouse with an antigen, wherein the genome of a germline mouse gene germ line comprises: one or more Vλ human gene segments and one or more Jλ human gene segments, wherein one or more Vλ human gene segments and one or more Jλ human gene segments substitute endogenous Vκ mouse gene segments and endogenous Jκ gene segments; and wherein one or more Vλ human gene segments and one or more Jλ human gene segments are operably linked to endogenous constant (Cκ) mouse κ light chain region; and (b) detecting a variable region of the λ human light chain which codes the variable λ light chain domain of a human in the antibody which specifically binds to the antigen and is generated by a genetically modified mouse, wherein the λ human light chain variable region is derived from a Vλ human gene segment, from one or more Vλ human gene segments and a Jλ human gene segment, from one or more Jλ human gene segments. Also described is a method of producing a variable domain of an λ human light chain, involving: (a) immunising a genetically modified mouse with an antigen, wherein the genetically modified mouse germline genome comprises: one or more Vλ human gene segments and one or more Jλ human gene segments, wherein one or more Vλ human gene segments and one or more Jλ human gene segments substitute endogenous Vκ mouse gene segments and endogenous Jκ gene segments; and wherein one or more Vλ human gene segments and one or more Jλ human gene segments are operably linked to endogenous mouse Cκ gene; and (b) detecting a variable λ light chain domain of a human in the antibody which specifically binds to the antigen and has been generated by a genetically modified mouse.
EFFECT: there are presented mice expressing a light chain with a λ human variable region and a constant mouse region.
24 cl, 13 dwg, 8 tbl, 7 ex
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Authors
Dates
2020-06-25—Published
2011-06-22—Filed