Human Lambda Light Chain Mice

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 making an antibody comprising a human λ variable domain, the method comprising the steps of:
(a) exposing a genetically modified mouse to an antigen, wherein the genetically modified mouse has a genome comprises an immunoglobulin locus comprising human Vλ and Jλ gene segments operably linked to a mouse Cκ gene such that the mouse expresses an immunoglobulin light chain that comprises a human λ variable domain derived from the Vλ and Jλ gene segments fused with a mouse κ constant domain; (b) allowing the genetically modified mouse to develop an immune response to the antigen; and (c) isolating from the mouse of (b) an antibody specific for the antigen, wherein the antibody comprises the human λ variable domain derived from the human Vλ and Jλ gene segments.