Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies

A method of obtaining an antigen-specific antibody or antigen binding fragment thereof, said antibody comprising a human immunoglobulin heavy (IgH) chain comprising a human IgH chain variable region and a human IgH chain constant region, said antigen binding fragment comprising said human IgH chain variable region, the method comprising:

• expressing said antibody or antigen binding fragment thereof from a cell comprising nucleic acid encoding said human IgH chain variable region of said antibody,
• wherein said human IgH chain variable region is of a mouse whose genome comprises a gene locus for expression of antibody heavy chains, said locus comprising:
• (a) an unrearranged human heavy chain variable region comprising human heavy chain variable region gene segments comprising a plurality of unrearranged human variable gene segments (VH), one or more unrearranged human D gene segments (D) and one or more human JH gene segments (JH) for expression of a plurality of human heavy chain variable domains;
• and (b) one or more human gamma heavy chain constant regions comprising gamma heavy chain constant region gene segments comprising a human CH2 gene segment and a human CH3 gene segment encoding gamma antibody heavy chains comprising (i) gamma heavy chain constant domains and (ii) human heavy chain variable domains;
• wherein said unrearranged human heavy chain variable region of said mouse is upstream of and operably linked to said gamma heavy chain constant region and comprised by an IgH locus, and wherein said human CH2 and human CH3 gene segments are selected from the group consisting of
• (i) a human IGHG1*01 CH2 gene segment and a human IGHG1*01 CH3 gene segment,
• (ii) a human IGHG2*01 CH2 gene segment and a human IGHG2*01 CH3 gene segment,
• (iii) a human IGHG3*01 CH2 gene segment and a human IGHG3*01 CH3 gene segment,
• (iv) a human IGHG3*03 CH2 gene segment and a human IGHG3*03 CH3 gene segment,
• (v) a human IGHG3*04 CH2 gene segment and a human IGHG3*04 CH3 gene segment
• and
• (vi) a human IGHG4*01 CH2 gene segment and a human IGHG4*01 CH3 gene segment, wherein the human CH2 and CH3 are in place of endogenous gamma heavy chain constant region DNA, such that said human heavy chain variable region gene segments are able to recombine for expression of an antibody heavy chain comprising a human gamma heavy chain antibody Fc region comprising a human gamma CH2 and a human gamma CH3 and a human heavy chain variable domain.