Transgenic D011.10 T Cell Receptor/Transgenic CAR

Constitutive Knockout

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The NIAID Exchange Program has closed and live production of this model has ceased. This webpage is retained for historical reference, but this model is not available from Taconic.

Model #
Genotype
Nomenclature

4285-F

ko/ko;ko/ko

BALB/cJ-Tg(DO11.10)10Dlo Tg(CARΔ-1)1Jdgr
4285-M

ko/ko;ko/ko

BALB/cJ-Tg(DO11.10)10Dlo Tg(CARΔ-1)1Jdgr

Model Description

The Transgenic DO11.10 T Cell Receptor/Transgenic CARΔ mice are homozygous for a transgene that expresses in the T cell compartment a human coxsackie/adenovirus receptor lacking a cytosolic domain (CARΔ-I). In addition, they are homozygous for the DO11.10 T cell receptor transgene that encodes a T cell receptor specific for a chicken ovalbumin (OVA) peptide, amino acids 323-339, presented by the MHC class II molecule I-Ad. The presence of the tailless CARΔ-I Tg does not affect lymphocyte development and it is highly expressed in T cells and to a lesser extent in B cells and immature CD4+CD8+ thymocytes. There is no significant expression of CAR on platelets, macrophages, red blood cells, or non-lymphoid tissues. While naive T cells are resistant to adenoviral infection, the expression of CAR on T cells enhances adenoviral- mediated gene expression in vitro and in vivo. The expression of the double Tg allows one to efficiently introduce genes of interest into the T cells of a mouse with a well-defined and specific T cell receptor giving one the ability to analyze a variety of pathways affecting lymphocyte physiology.

Origin:

The Transgenic DO11.10 T Cell Receptor/Transgenic CARΔ line was made by James DeGregori at the University of Colorado Health Science Center in 2000. A human CARΔ-I cDNA was cloned into the AscI-digested lckB proximal promoter/human CD2 enhancer transgene construct. CARΔ-I transgenic mice were then generated by pronuclear microinjection of this DNA construct into FVB/NJ zygotes The CAR positive mice were maintained by backcrossing onto BALB/cJ for greater than 10 generations. The CAR transgenic mice to were bred to BALB/cJ mice containing the DO11.10 transgene (created by K. Murphy and D. Loh). These mice were subsequently maintained by intracrossing for several generations. The double transgenic mice were transferred to the NIAID repository at Taconic in 2004 and after expansion, mice which tested positive for both Tgs using flow cytometry, were embryo transfer derived. These mice were then intracrossed and mice homozygous for both the TCR DO11.10 and CARΔ-I transgenes were identified by test mating the mice to wild type partners and selecting animals that only gave rise to double transgene positive offspring.

Availability:

This model is no longer available.

Color:

Albino

Species:

Mouse

Initial Publication:

Leon RP, Hedlund T, Meech SJ, Li S, Schaack J, Hunger SP, Duke RC, DeGregori J: Adenoviral-mediated gene transfer in lymphocytes. PNAS USA vol. 95, pp. 13519-13164 1998.

Wan YY, Leon RP, Marks R, Cham CM, Schaack J, Gajewski TF, DeGregori J: Transgenic expression of the coxsackie/adenovirus receptor enables adenoviral-mediated gene delivery in naïve T cells. PNAS USA vol. 97, pp. 13784-13789 2000.

Wan YY and DeGregori J: The survival of antigen-stimulated T cells require NFkB-mediated inhibition of p73 expression. Immunity vol. 18, pp. 331-342 2003.

Murphy KM, Heimberger, and Loh DY: Induction by antigen of intrathymic apoptosis of CD4+ CD8+ TCRlo thymocytes in vivo. Science 250, pp. 1720-1723 1990