Patent ID: 8507748

Claim:
A method for the production of a single heavy chain antibody comprising: (i) immunizing a transgenic mouse whose genome comprises a heterologous VHH heavy chain locus with an antigen, wherein the heterologous VHH heavy chain locus comprises: (a) at least one VHH exon, at least one D exon and at least one J exon, wherein the VHH exon, the D exon and the J exon are capable of recombining to form a VDJ coding sequence, and wherein the VHH exon comprises a naturally occurring camelid VHH coding sequence, (b) at least one constant heavy chain region comprising at least one constant heavy chain gene, wherein each of said at least one constant heavy chain gene, when expressed, does not express a functional CH1 domain, and (c) a locus control region providing for expression of the VHH heavy chain locus specifically in B cells, wherein said mouse expresses the VHH heavy chain locus in B cells in response to antigen challenge; and (ii) isolating single heavy chain antibody against said antigen.