Method of cloning a lambda light chain variable domain using a human lambda light chain mouse

摘要

Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.

主权项

1. A method for cloning a λ light chain variable domain, comprising the steps of:
(a) obtaining a cell from a transgenic mouse whose genome comprises an endogenous κ light chain immunoglobulin locus comprising a replacement of endogenous Vκ and Jκ gene segments with human Vλ and Jλ gene segments, wherein the human Vλ and Jλ gene segments are operably linked to a mouse Cκ gene such that the mouse expresses an immunoglobulin light chain that comprises a human λ variable region nucleic acid sequence fused with a mouse κ constant region nucleic acid sequence; (b) cloning a λ light chain variable domain derived from the human Vλ and Jλ gene segments.