These NOD.clone-4 TCR mice express a T cell receptor specific for influenza virus A/PR/8 hemagglutinin in the context of the MHC class I molecule H2-Kd. The presence of Thy1a serves as a marker for following donor CD8+ T cells in vitro.
Linda Sherman, The Scripps Research Institute
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Not Applicable | Thy1 | thymus cell antigen 1, theta |
Allele Type |
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Transgenic (Inserted expressed sequence) |
Transgenic mice, commonly referred to as NOD.clone-4 TCR, are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities. The TCR expressed from this transgene is specific for influenza virus A/PR/8 hemagglutinin (HA) in the context of the MHC class I molecule H2-Kd. FACS analysis of pancreatic lymph node indicates CFSE treated NOD clone-4 T cells adoptively transferred into NOD.InsHA (Stock No. 005685) proliferate vigorously and there is a 2-3-fold increase in the percentage of dividing clone-4 TCR, CD8+ T cells when compared to BALB/cBy (Stock Nos. 005307 and 005533) or B10.D2 (Stock Nos. 005308 and 005534). HA specific reactivity not tolerance is observed.
This mouse is further modified with the Thy1a allele, rather than the alternate allele Thy1b present in C57BL/10, DBA/2, BALB/c and NOD/Lt mice. Thus, cell populations derived from these transgenic mice can be distinguished from syngeneic host and other mice with the alternate allele via flow cytometry. The presence of Thy1a serves as a marker for following donor CD8+ T cells in vitro.
This transgenic model is useful in the study of T-cell recognition of defined antigen, specifically HA, in the islets of NOD-InsHA mice.
The Tcra and Tcrb transgenes encode a Tcr cDNA from Clone 4 derived from a B10.D2-Hc1 H2d H2-T18c/nSn mouse previously immunized with Influenza virus A/PR/8. The clone 4 transgenic constructs were co-injected and co-inserted in (C57BL/6 x BALB/c)F1 oocytes. Transgene positive mice were backcrossed to BALB/cBy-Thy1a congenic prior to crossing to NOD/Lt for 19 generations. In 2005, The Jackson Laboratory imported this transgenic strain at generation N19F4. Upon arrival the strain was mated to NOD/LtJ (stock No. 001976) prior to mating Tg/? x Tg/?. FACS analysis performed at The Jackson Laboratory confirms Thy1a allele is homozygous.
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 | T-cells. |
Allele Name | a variant |
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Allele Type | Not Applicable |
Allele Synonym(s) | thetaAKR; theta-AKR; Thy1.1; Thy-1.1; Thy1a |
Gene Symbol and Name | Thy1, thymus cell antigen 1, theta |
Gene Synonym(s) | |
Site of Expression | The Thy1 locus determines a surface antigen present on cells of the thymus, a number of mouse leukemias, brain, and in lesser amounts on lymph node and spleen cells. |
Strain of Origin | Not Applicable |
Chromosome | 9 |
General Note | The Thy1 locus determines a surface antigen present on cells of the thymus, a number of mouse leukemias, brain, and in lesser amounts on lymph node and spleen cells. The allele Thy1a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains; the allele Thy1b determines an antigenic specificity, Thy-1.2, found in the C3HeB/Fe and many other strains (J:5243, J:5012, J:4469). The Thy1 antigen is probably present on all T lymphocytes and absent from all B lymphocytes, and it thus serves as a valuable T-cell marker (J:5243). It is very widely used in experiments designed to determine the distribution and function of T-cells. Thy1 specifies a T-cell surface glycoprotein, T25, with a molecular weight of 25 kDa (J:5707). The protein appears to be anchored in the cell membrane by a lipid that is either phosphotidylinositol or closely related to it (J:12016). Thy1 may function in the cell membrane as a signal transduction molecule (J:8333). The Thy1 locus, or possibly a gene closely linked to it, controls quantitative expression of a protein that is the same size as Thy1 and is expressed on thymus and brain but not on lymph node and spleen cells (J:7900). |
Molecular Note | The allele Thy1a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains. |
Allele Name | transgene insertion 1, Linda Sherman |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | (HA)-TCR; C4; CL4; CL-4; CL-4 TCR; CL4-TCR; Clone 4; clone 4 TCR; Clone-4 TCR |
Gene Symbol and Name | Tg(TcraCl4,TcrbCl4)1Shrm, transgene insertion 1, Linda Sherman |
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 |
Site of Expression | T-cells. |
Strain of Origin | (C57BL/6 x BALB/c)F1 |
Chromosome | UN |
Molecular Note | Tcra and Tcrb cDNAs were isolated from Clone-4, a CTL line derived from a B10.D2-Hc1 H2d H2-t18c/nSnJ mouse immunized with influenza virus A/PR/8. A Tcra cDNA fragment representing the V-J exon, containing Valpha10, was cloned into a Tcra shuttle vector that includes a mouse Tcra-V promoter, the immunoglobulin heavy-chain enhancer EH, and the Tcra-C genes with some flanking DNA. Likewise, a Tcrb cDNA fragment representing the VDJ exon, containing Vbeta8.2, was cloned into a Tcrb shuttle vector including a mouse Tcrb-V promoter, EH, and the Tcrb-C genes with some flanking DNA. The plasmid constructs were coinjected. This transgenic TCR specifically recognizes influenza virus A/PR/8 hemagglutinin restricted by MHC class I H2kd. |
Mutations Made By | Linda Sherman, The Scripps Research Institute |
When using the NOD.Thy1a-Clone 4 TCR mouse strain in a publication, please cite the originating article(s) and include JAX stock #005686 in your Materials and Methods section.
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Hemizygous or Non carrierfor Tg(TcraCl4,TcrbCl4)1Shrm |
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