Nomenclature: B6.129S2-H2-Ab1^tm1Gru Tg(HLA-DRA/H2-Ea,HLA-DRB1^*0401/H2-Eb)1Kito

The HLA-DR4 allele is associated with the development of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. In an attempt to provide a mouse model for these diseases, a hybrid MHC class II molecule between the peptide binding domains of human HLA-DRA and HLA-DRB*0401 and the membrane proximal domains of mouse I-E (H2-E) was engineered and co-injected into C57BL/6 fertilized eggs. The transgenic offspring were bred to a mouse incapable of expressing other MHC class II molecules (Abb knockout on B6 background). By preserving the alpha 2 and beta 2 domains of mouse MHC class II, interactions with CD4 co-receptors on T cells was preserved. This mouse is healthy and breeds normally. Immunization with a peptide from a proteolipid protein known to bind to HLA-DR4, provoked a strong T cell proliferative response, caused inflammatory lesions in CNS white matter, and symptoms of experimental allergic encephalomyelitis (EAE).

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