Patent ID: 9686970
Date: 2017-06-27
CPC Classifications: A01K,C07K,C12N

Claim:
1. A mouse whose germline genome comprises (a) a modified endogenous mouse immunoglobulin heavy chain locus comprising a replacement of all functional endogenous mouse immunoglobulin heavy chain variable (V wherein the first nucleotide sequence is operably linked to an intact mouse immunoglobulin heavy chain constant (C (b) a modified endogenous immunoglobulin light chain κ locus comprising a replacement of all functional endogenous mouse immunoglobulin light chain Vκ gene segments and all functional endogenous mouse light chain Jκ gene segments at the endogenous mouse immunoglobulin light chain κ locus with a second nucleotide sequence that comprises (i) a second plurality of unrearranged functional human immunoglobulin light chain variable κ (hVκ) gene segments and (ii) all five unrearranged functional human immunoglobulin light chain joining gene segments (hJκ1-hJκ5), wherein the second nucleotide sequence is operably linked to an intact mouse immunoglobulin light chain κ constant (Cκ) region nucleic acid sequence at the endogenous mouse light chain κ immunoglobulin locus; wherein in a B cell during B cell development the first nucleotide sequence rearranges to form a first rearranged human immunoglobulin light chain variable Vκ/Jκ nucleotide sequence operably linked to the intact mouse immunoglobulin heavy chain constant region nucleic acid sequence at the endogenous mouse immunoglobulin heavy chain locus, and the second nucleotide sequence rearranges to form a second rearranged human immunoglobulin light chain variable region Vκ/Jκ nucleotide sequence operably linked to the intact mouse immunoglobulin light chain κ constant region nucleic acid sequence at the endogenous mouse κ light chain immunoglobulin locus, and wherein the mouse further comprises a CD19