These NOD.TcrLCMV mice express a transgene containing Tcrα and TcrΒ gene segments.
Dr. David Serreze, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
These NOD.TcrLCMV mice carry a T-cell receptor (Tcra-V2, Tcra-J TA31 / Tcrb-V8.1, Tcrb-D, Tcrb-J 2.4) specific for MHC Class I restricted H2-Db peptide from LCMV (lymphocytic choriomeningitis virus). These mice undergo positive selection for the LCMV T cell receptor due to the MHC Class I H2-Db gene of the NOD. Because the LCMV antigen is not present normally in the NOD mouse, the majority of T cells (81%), which express the LCMV specific T cell receptor are irrelevant. Despite this, these transgenic mice become diabetic with the same incidence as NOD/Lt controls (90% female incidence after 30 weeks), indicating that the non-transgenic T cells (19%) sufficiently expand for diabetogenisis. Additionally, NOD.TcrLCMV have higher total number of transgenic and non-transgenic T cells than the control stock, B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ (Stock No. 004694). Therefore, T cells are accumulating in absence of their related peptide antigen, demonstrating that the NOD background promotes antigen independent T cell expansion.
In 2004-2005, The Jackson Laboratory diabetes incidence for this NOD.TcrLCMV strain was 50% by ~15 weeks for females and ~22 weeks for males.
Mice on the NOD/ShiLtJ inbred background (Stock No. 001976) develop spontaneous autoimmune Type 1 diabetes. As such, these NOD.TcrLCMV mice may be given Complete Freund's Adjuvant (CFA) prior to six weeks of age to delay diabetes onset.
Zinkernagel et al, established a set of LCMV-specific cytotoxic T-cell clones from lethally irradiated B10.BR/SgSn (H-2K) reconstituted with T-cell depleted C57BL/10Sn (H-2b) bone marrow cells. The variable beta chain from clone P14, containing Tcrb-V8.1, TcrB-D, TcrB-J2.4 gene segments under the control of the H-2Kb promoter and variable alpha chain from the P14 clone, containing Tcra-V2 and Tcra-J TA31 gene segments under the control of the H-2Kb promoter were co-injected into B6D2F2 fertilized embryos. 10-20 copies of both the alpha and beta transgenes co-integrated on the same chromosome in male founder number 327. Founder 327 was backcrossed to C57BL/6J for one generation prior to being intercrossed to make homozygotes strain. Serezze, et al. obtained JR2331-B6;D2-Tg(TcrLCMV)327Sdz/J mice, backcrossed to NOD/Lt for 9 generations and then mated Tg/? x Tg/?. A genome scan for NOD derived Idd loci was done as described in J. Exp. Med. 1996 184:2049. This T cell receptor is specific for an LCMV peptide in the context of H2-Db and requires the presence of H2-Db to be positively selected. (Serreze et al., Diabetes, 2001.). In 2003, the T1DR received NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ from Dr. Serezze. This strain is maintained Tg/? x Tg/?
Expressed Gene | Tcrb, T cell receptor beta chain, mouse, laboratory |
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Expressed Gene | Tcra, T cell receptor alpha chain, mouse, laboratory |
Site of Expression |
Allele Name | transgene insertion 327, Birgit Ledermann |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | P14; P14 TCR; P14 TCR-alphabeta (Valpha2Vbeta8.1); P14 TCRValpha2Vbeta8; P14-TCR; TCR LCMV; TCR P14; TCR-Tg; TgTcr |
Gene Symbol and Name | Tg(TcrLCMV)327Sdz, transgene insertion 327, Birgit Ledermann |
Gene Synonym(s) | |
Promoter | Tcrb, T cell receptor beta chain, mouse, laboratory |
Promoter | Tcra, T cell receptor alpha chain, mouse, laboratory |
Expressed Gene | Tcrb, T cell receptor beta chain, mouse, laboratory |
Expressed Gene | Tcra, T cell receptor alpha chain, mouse, laboratory |
Strain of Origin | (C57BL/6 x DBA/2)F2 |
Chromosome | UN |
General Note | Transgenic mice carry a T-cell receptor (Tcra-V2, Tcra-J TA31 / Tcrb-V8.1, Tcrb-D, Tcrb-J 2.4) specific for the gp33 protein of LCMV (lymphocytic choriomeningitis virus), H2-Db. |
Molecular Note | The transgene carries both Tcra and Tcrb. Ten to twenty copies of the Tcr transgene were reported to have integrated on the same chromosome. At least two transgenic lines are known to exist. Line 327 is the representative line. The second line is 318. |
Mutations Made By | Dr. Rolf Zinkernagel, University of Zurich |
This strain is maintained Tg/? x Tg/?.
Mice on the NOD/ShiLtJ inbred background (Stock No. 001976) develop spontaneous autoimmune Type 1 diabetes. As such, these NOD.TcrLCMV mice may be given Complete Freund's Adjuvant (CFA) prior to six weeks of age to delay diabetes onset.
When using the NOD.TcrLCMV mouse strain in a publication, please cite the originating article(s) and include JAX stock #004696 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Tg(TcrLCMV)327Sdz, 1 pair minimum |
Frozen Mouse Embryo | NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ Frozen Embryos | $3373.50 |
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