A method of obtaining a human immunoglobulin heavy chain variable region sequence from a mouse, wherein the human immunoglobulin heavy chain variable region sequence is derived from a human V H 1-69 gene segment or a human V H 1-2 gene segment, wherein the method comprises: (a) immunizing a mouse with an antigen of interest, wherein the mouse comprises in its genome: (i) an unrearranged human genomic sequence comprising a single human V H gene segment, one or more human D H gene segments, and one or more human J H gene segments, wherein the single human V H gene segment, one or more human D H gene segments, and one or more human J H gene segments are operably linked to a mouse immunoglobulin heavy chain constant region gene, and wherein the single human V H gene segment is V H 1-2, V H 1-69 or a polymorphic variant thereof; and (ii) a sequence that encodes a mouse ADAM6a protein or a functional fragment thereof and a sequence that encodes a mouse ADAM6b protein or a functional fragment thereof, wherein the mouse ADAM6a protein or functional fragment thereof and the mouse ADAM6b protein or functional fragment thereof are functional in a male mouse, wherein said encoding sequences are located at a position different than an ADAM6 locus of a wild-type mouse; and wherein the mouse is incapable of forming an immunoglobulin heavy chain variable region sequence that is not derived from a human V H 1-69 gene segment or a human V H 1-2 gene segment; (b) allowing the mouse to mount an immune response with respect to the antigen of interest; and (c) identifying or isolating a human immunoglobulin heavy chain variable region sequence from the mouse, wherein the human immunoglobulin heavy chain variable region sequence encodes a human immunoglobulin heavy chain variable domain of antibody that binds to the antigen of interest. (a) immunizing a mouse with an antigen of interest, wherein the mouse comprises in its genome: (i) an unrearranged human genomic sequence comprising a single human V H gene segment, one or more human D H gene segments, and one or more human J H gene segments, wherein the single human V H gene segment, one or more human D H gene segments, and one or more human J H gene segments are operably linked to a mouse immunoglobulin heavy chain constant region gene, and wherein the single human V H gene segment is V H 1-2, V H 1-69 or a polymorphic variant thereof; and (ii) a sequence that encodes a mouse ADAM6a protein or a functional fragment thereof and a sequence that encodes a mouse ADAM6b protein or a functional fragment thereof, wherein the mouse ADAM6a protein or functional fragment thereof and the mouse ADAM6b protein or functional fragment thereof are functional in a male mouse, wherein said encoding sequences are located at a position different than an ADAM6 locus of a wild-type mouse; and wherein the mouse is incapable of forming an immunoglobulin heavy chain variable region sequence that is not derived from a human V H 1-69 gene segment or a human V H 1-2 gene segment; (i) an unrearranged human genomic sequence comprising a single human V H gene segment, one or more human D H gene segments, and one or more human J H gene segments, wherein the single human V H gene segment, one or more human D H gene segments, and one or more human J H gene segments are operably linked to a mouse immunoglobulin heavy chain constant region gene, and wherein the single human V H gene segment is V H 1-2, V H 1-69 or a polymorphic variant thereof; and (ii) a sequence that encodes a mouse ADAM6a protein or a functional fragment thereof and a sequence that encodes a mouse ADAM6b protein or a functional fragment thereof, wherein the mouse ADAM6a protein or functional fragment thereof and the mouse ADAM6b protein or functional fragment thereof are functional in a male mouse, wherein said encoding sequences are located at a position different than an ADAM6 locus of a wild-type mouse; and (b) allowing the mouse to mount an immune response with respect to the antigen of interest; and (c) identifying or isolating a human immunoglobulin heavy chain variable region sequence from the mouse, wherein the human immunoglobulin heavy chain variable region sequence encodes a human immunoglobulin heavy chain variable domain of antibody that binds to the antigen of interest.