NOD.Cg-Thy1^a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ

Stock number: 005686
Product name: NOD.Thy1^a-Clone 4 TCR
Research areas: Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

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-K^d. The presence of Thy1^a serves as a marker for following donor CD8⁺ T cells in vitro.

Detailed description

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-K^d. 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 Thy1^a allele, rather than the alternate allele Thy1^b 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 Thy1^a 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.

Development

The Tcra and Tcrb transgenes encode a Tcr cDNA from Clone 4 derived from a B10.D2-Hc¹ H2^d H2-T18^c/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-Thy1^a 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 Thy1^a allele is homozygous.

Allele

Symbol: Tg(TcraCl4,TcrbCl4)1Shrm
Name: transgene insertion 1, Linda Sherman
MGI accession ID: MGI:3586582
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcraCl4,TcrbCl4)1Shrm
Marker name: transgene insertion 1, Linda Sherman
Chromosome: UN
Strain of origin: (C57BL/6 x BALB/c)F1
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Site of expression: T-cells.
Molecular note: Tcra and Tcrb cDNAs were isolated from Clone-4, a CTL line derived from a B10.D2-Hc¹ H2^d H2-t18^c/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 E_H, 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, E_H, 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 H2k^d.

Allele

Symbol: Thy1^a
Name: a variant
MGI accession ID: MGI:3579311
Generation method: Not Applicable
Marker symbol: Thy1
Marker name: thymus cell antigen 1, theta
Chromosome: 9
Strain of origin: Not Applicable
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.
Molecular note: The allele Thy1^a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains.
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 Thy1^a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains; the allele Thy1^b 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).