Tg(IGH@yH2CM)2Amgn

A yeast artificial chromosome (YAC) was constructed from human germline sequence of the immunoglobulin heavy chain gene cluster. This YAC consisted of 66 V-heavy gene segments, all 30 D gene segments, all 6 J segments, the C-mu, and the C-delta gene segments from the human locus. Downstream of this, the mouse sequence encoding the class switch recombination recognition site of gamma1 heavy chain (from the Ighg1 gene) replaced the equivalent human sequence. Downstream of this, the human exons encoding the constant region of gamma4 heavy chain were placed. A murine enhancer element were located at the 3' end of the construct. Southern blot analysis confirmed that the YAC inserted into ES cells without any recombination events. Two transgenic lines were created with line 1 having the highest expression of antibodies containing human IgG4 after immunization. (J:139792)