NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ

Stock number: 004696
Product name: NOD.TcrLCMV
Research areas: Research Tools

Description

These NOD.TcrLCMV mice express a transgene containing Tcrα and TcrΒ gene segments.

Detailed description

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-D^b peptide from LCMV (lymphocytic choriomeningitis virus). These mice undergo positive selection for the LCMV T cell receptor due to the MHC Class I H2-D^b 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.

Development

Zinkernagel et al, established a set of LCMV-specific cytotoxic T-cell clones from lethally irradiated B10.BR/SgSn (H-2^K) reconstituted with T-cell depleted C57BL/10Sn (H-2^b) 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-2K^b promoter and variable alpha chain from the P14 clone, containing Tcra-V2 and Tcra-J TA31 gene segments under the control of the H-2K^b 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-D^b and requires the presence of H2-D^b 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/?

Allele

Symbol: Tg(TcrLCMV)327Sdz
Name: transgene insertion 327, Birgit Ledermann
MGI accession ID: MGI:2665105
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcrLCMV)327Sdz
Marker name: transgene insertion 327, Birgit Ledermann
Chromosome: UN
Strain of origin: (C57BL/6 x DBA/2)F2
Expressed genes: Tcrb,T cell receptor beta chain,mouse, laboratory; Tcra,T cell receptor alpha chain,mouse, laboratory
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.
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-D^b.