Abb Knockout/Transgenic HLA-DR4

Constitutive Knock Out/Random Transgenic

Abb Knockout/Transgenic HLA-DR4 Constitutive Knock Out/Random Transgenic Mouse Model

C57BL/6 Background

  • Model #
  • Genotype
  • Nomenclature
  • 4149-F
    B6.129S2-H2-Ab1tm1Gru Tg(HLA-DRA/H2-Ea,HLA-DRB1*0401/H2-Eb)1Kito
  • 4149-M
    B6.129S2-H2-Ab1tm1Gru 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).

Genetic Background:

C57BL/6 Background


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.





Initial Publication:

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.

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Taconic Transgenic Models™ (Models) are produced and distributed under rights to patents and intellectual property licensed from various institutions. Taconic sells the Models to purchasers, grants to each purchaser a right under Taconic's rights in such licensed patents and intellectual property to use the purchased Model in consideration of purchasers' acknowledgement of and agreement to the Terms and Conditions of Sale and the following terms of use:

  • Title to these Models and biological materials derived from them remains with Taconic Biosciences, Inc.
  • The Models will be used for research purposes only.
  • The Models will not be bred except to obtain embryos or fetuses required for research purposes
  • The Models and biological materials derived from them will not be distributed to third parties or used for commercial purposes.