The Rag2 Knockout/Transgenic Cyt5CC7 T Cell Receptor line is homozygous for a transgene that encodes a T cell receptor that is specific for a pigeon cytochrome c peptide, amino acids 81-104, presented by the MHC class II molecule I-Ea/k. It is also deficient in the Rag2 gene (recombinase activating gene 2) and therefore does not develop endogenous mature T or B cells. Most of the T cells in the periphery are CD4+ but there also is a tiny fraction of CD8+ T cells expressing the transgene. The depletion of endogenous T and B cells causes a proportional enrichment of NK cells in the spleen. These mice are useful for in vitro studies of CD4+ T cell differentiation into TH1 and TH2 populations and as a source of donor cells for adoptive transfer into B10.A mice for in vivo studies of inflammation and tolerance. Applications include studies of inflammation, tolerance, and T cell development.
Genetic Background: B10.A Background
Origin: The Transgenic Cyt5CC7 T Cell Receptor mice were made by Dr. Barbara Fazekis de St. Groth and colleagues in 1992 at Stanford University using B10B6F1 donor embryos. The founder line I was transferred to the NIAID in 1992 and backcrossed for multiple generations to the B10.A congenic strain. The line was transferred to the NIAID Repository at Taconic in 1995 and embryo transfer derived. In 1996, the B10.A/Ai-Tg(Tcra5CC7,Tcrb5CC7)Iwep mice were intercrossed with homozygote Rag2 knockout mice on a congenic B10.D2 background (received at Taconic into the NIAID Repository in 1995 by ET derivation). The resulting F1 pups were mated to the B10.A/Ai-Tg(Tcra5CC7,Tcrb5CC7)Iwep once more and B10.A homozygotes were selected by typing with anti-H-2K antibodies. They were then intracrossed and Rag2 homozygotes identified by an absence of B220+ B cells. Mice homozygous for the transgene were then selected in further matings which included test crosses to wild type mice to identify Valpha11 homozygotes. These mice have bred true for the transgenic T cell receptor (TCR), Rag2-/-, Kk since June 1997. In multiple functional experiments the mice also have expressed the Ek restriction element (i.e. I-Ek MHC molecule). Finally recent examination of the T1 polymorphism in the TL region by SSCP analysis has shown this locus to also be derived from the B10.A allele.
Seder RA, Paul WE, Davis MM, Fazekas de St Groth B; The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.
; J Exp Med 1992 Oct 1;176(4):1091-1098
Shinkai, Y, Rathbun, G, Lam, KP, Oltz, EM, Stewart, V, Mendelsohn, M, Charron, J, Datta, M, Young, F, Stall, AM, and Alt, FW. (1992) RAG-2-Deficient Mice Lack Mature Lymphocytes Owing to Inability to Initiate V(D)J Rearrangement
, Cell, 68: 855-867