The antigen-binding domains of HLA-DRA and HLA-DRB1*0401 (representative of the DR4 supertype) were attached to the membrane-proximal domains of I-Ed alpha and I-Ed beta (H2-E), respectively, by replacing exon 2 of the mouse genes with exon 2 of the human genes. These constructs were then microinjected into C57BL/6 fertilized eggs. Transgenic founders were then crossed to MHC class II deficient mice: the GenPharm C2d line, now known as the Taconic Transgenic Model B6.129-H2-Ab1tm1Gru, which has the I-A beta gene inactivated by gene targeting in 129S2-derived ES cells and the unexpressed I-E alpha allele found in the C57BL/6 haplotype. Mice expressing HLA-DR and not endogenous I-E beta were selected to create the line (J18). The chimeric molecules were shown to have the same peptide binding specificity as HLA-DRB1*0401 molecules. The line was received at Taconic for the NIAID repository in 1998 and rederived via embryo transfer.
Ito K, Bian HJ, Molina M, Han J, Magram J, Saar E, Belunis C, Bolin DR, Arceo R, Campbell R, Falcioni F, Vidovic D, Hammer J, Nagy ZA: HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis. J Exp Med 1996 Jun 1;183(6):2635-44.
Grusby MJ, Johnson RS, Papaioannou VE, Glimcher LH. (1991) Depletion of CD4+ T-Cells in Major Histocompatibility Complex Class II - Deficient Mice. Science, 253(5026):1417-1420.