Non-human animals having a mutant kynureninase gene

A method of producing an antibody in a rodent, the method comprising the steps of

• (a) immunizing a rodent with an antigen, which rodent has a genome comprising a mutant kynureninase (Kynu) gene that encodes a Kynu polypeptide having a D93E substitution;
• (b) maintaining the rodent under conditions sufficient that the rodent produces an immune response to the antigen;
• and
• (c) recovering an antibody from the rodent, or a rodent cell, that binds the antigen.

A rodent whose genome comprises

• (i) a mutant Kynu gene, which mutant kynureninase (Kynu) gene comprises one or more point mutations in exon three and encodes a Kynu polypeptide having a D93E substitution;
• (ii) an insertion of a human immunoglobulin heavy chain variable region that includes one or more human VH segments, one or more human DH segments and one or more human JH segments, which human immunoglobulin heavy chain variable region is operably linked to an endogenous rodent immunoglobulin heavy chain constant region;
• and
• (ii) an insertion of a human immunoglobulin light chain variable region that includes one or more human VL segments and one or more human JL segments, which human immunoglobulin light chain variable region is operably linked to an endogenous rodent immunoglobulin light chain constant region.

A method of producing an antibody in a rodent, the method comprising the steps of

• (a) immunizing a rodent with the membrane proximal external region (MPER) of HIV-1 gp4, in whole or in part, which rodent has a genome comprising
• (i) a mutant Kynu gene that includes one or more point mutations in exon three and encodes a Kynu polypeptide having a D93E substitution;
• (ii) an insertion of a human immunoglobulin heavy chain variable region that includes one or more human VH segments, one or more human DH segments and one or more human JH segments, which human immunoglobulin heavy chain variable region is operably linked to an endogenous rodent immunoglobulin heavy chain constant region;
• and
• (ii) an insertion of a human immunoglobulin light chain variable region that includes one or more human VL segments and one or more human JL segments, which human immunoglobulin light chain variable region is operably linked to an endogenous rodent immunoglobulin light chain constant region.
• (b) maintaining the rodent under conditions sufficient that the rodent produces an immune response to the MPER of HIV-1 gp41, in whole or in part;
• and
• (c) recovering an antibody from the rodent, or a rodent cell, that binds the MPER of HIV-1 gp41;
• wherein the antibody comprises immunoglobulin heavy chains that include human VH domains linked to rodent CH domains, and immunoglobulin light chains that include human Vκ domains linked to rodent Cκ domains.