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Strain Name:

B6.Cg-Thy1a/Cy Tg(TcraTcrb)8Rest/J

Stock Number:

005023

Availability:

Repository- Live


General Terms and Conditions

Former Name      B6.Cg Thy1a-Tg(TcraTcrb)8Rest/J    (Changed: 15-DEC-04 )
      C57BL/6-Tg(TcraTcrb)8Rest/J    (Changed: 15-DEC-04 )
      pmel-1    (Changed: 15-DEC-04 )
Genes & Alleles   Tcra;   Tcrb;   Thy1;   Thy1a;   Tg(TcraTcrb)8Rest;


Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Nicholas Restifo,   National Cancer Institute
GenerationN?+N1F7 (19-DEC-07)

Strain Description
This transgenic strain carries a rearranged T cell receptor transgene specific for the mouse homologue (pmel-17) of human SILV (gp100), an enzyme involved in pigment synthesis that is expressed by the majority of malignant melanoma cells including B16 melanoma, as well as by normal melanocytes. The strain is also homozygous for the T lymphocyte specific Thy1a (Thy1.1) allele. CD8+ T cells express a Tcra-V1/Tcrb-V13- transgenic TCR that recognizes an epitope of pmel-17 corresponding to amino acids 25-33 of gp100 presented by H2-Db MHC class I molecules. Greater than 95% of the CD8+ T cells in transgenic mice expressed the transgenic TCR based on the expression of Vbeta13, amounting to about 20% of all splenocytes. T cells in blood and spleen generally expressed baseline levels of the activation/effector markers CD25, CD44, and CD69, indicating that most of the transgenic cells were in the naive state. These transgenic mice in conjunction with the poorly immunogenic B16 melanoma, a highly aggressive tumor in C57BL/6 mice, provide a physiologically relevant tumor model system for studies related to immunotherapy. In addition, these transgenic mice are useful for studying in vivo T-cell biology such as TCR-ligand interactions, T-cell activation, thymic selection, cross-presentation of antigens, process of thymic selection and central and peripheral T-cell tolerance and induction.

Strain Development
Transgenic constructs containing rearranged alpha-chain and beta-chain of the T-cell receptor specific for the mouse homologue (pmel-17) of human SILV (gp100) was co-injected into fertilized C57BL/6 mouse eggs. Founder animals were bred to C57BL/6 mice, and then crossed with B6.PL-Thy1a/CyJ (Stock No.00406) mice.

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tg(TcraTcrb)8Rest/?

        C57BL/6-Tg(TcraTcrb)8Rest
  • immune system phenotype
  • abnormal CD8-positive, alpha-beta cytotoxic T cell morphology (MGI Ref ID J:85058)
    • over 95 % of the CD8 T cells present in circulation express the transgenic TCR that is specific for the H2-Db restricted epitope of Silv (gp100), a protein that is highly expressed in melanoma cells
    • these transgenic T cells constitute about 20% of spleen cells
    • the baseline levels of activation markers for the transgenic T cells indicate that most of cells are in a naïve state
  • abnormal cytotoxic T cell physiology (MGI Ref ID J:85058)
    • upon in vitro stimulation with the immunogenic epitope of gp100, CD8 T cells are activated and proliferate extensively
  • increased interferon-gamma secretion (MGI Ref ID J:85058)
    • CD 8 T cells produce large amounts of IFN-gamma when cultured in the presence of melanoma cells
    • large number of IFN-gamma producing CD8 T cells are found in melanoma tumors that have regressed due to treatment with gp100 vaccine, IL-2, and adoptive transfer of transgenic CD8 T cells
  • tumorigenesis
  • altered tumor susceptibility/resistance (MGI Ref ID J:85058)
    • despite the presence of large number of anti-gp100 CD8 T cells, transplanted melanoma tumors that express gp100 have the same growth kinetics as tumors transplanted into control mice
    • adoptive transfer of transgenic splenocytes into normal mice bearing melanoma tumors also has no effect on tumor growth
    • there is a modest delay in tumor growth when mice that are recipients of transgenic T cells are also vaccinated with peptides that mimic the gp100 epitope
    • when IL-2 is administered with the vaccine, there is a large regression in tumor size in mice that are also recipients of transgenic T cells
    • mice bearing melanoma tumors that receive vaccine, transgenic T cells, and IL-2 have survival times of over 1 year compared to controls that die within 2 months
  • hematopoietic system phenotype
  • abnormal CD8-positive, alpha-beta cytotoxic T cell morphology (MGI Ref ID J:85058)
    • over 95 % of the CD8 T cells present in circulation express the transgenic TCR that is specific for the H2-Db restricted epitope of Silv (gp100), a protein that is highly expressed in melanoma cells
    • these transgenic T cells constitute about 20% of spleen cells
    • the baseline levels of activation markers for the transgenic T cells indicate that most of cells are in a naïve state

Gene & Allele Details

Allele Symbol Tg(TcraTcrb)8Rest
Allele Name transgene insertion 1, Nicholas Restifo
Common Name(s) Pmel-1;
Mutation Made By Marc Theoret,   NIH
Strain of OriginC57BL/6
Expressed Gene Tcrb, T-cell receptor beta chain, mouse, laboratory
Expressed Gene Tcra, T-cell receptor alpha chain, mouse, laboratory
Molecular Note These coinjected transgenes encode an H2-Db-restricted Valpha1 Vbeta13 T-cell receptor that recognizes a peptide comprising amino acids 25-33 of the protein known as pmel-17/gp100, a pigment biosynthetic enzyme that is encoded by the mouse Si (silver) gene and is expressed both in normal melanocytes and in malignant melanoma. [MGI Ref ID J:85058]
 
Allele Symbol Thy1a
Allele Name a variant
Common Name(s) Thy-1.1; Thy1.1; Thy1a;
Gene Symbol and Name Thy1, thymus cell antigen 1, theta
Chromosome 9
Gene Common Name(s) CD7; CD90; FLJ33325; T25; Thy 1.2; Thy-1; Thy-1.2; Thy1.1; Thy1.2;
General Note

The Thy1 locus determines an 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 experimentsdesigned 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).

Control Information

  Control
   000406 B6.PL-Thy1a/CyJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(TcraTcrb)8Rest
Tg(TcraTcrb)8Rest QPCR

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Thy1a     (14 strains)

Strains carrying other alleles of Tcra
005308   B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005895   B10.Cg-Thy1a H2d Tg(TcraCl1,TcrbCl1)1Shrm/J
002761   B10.Cg-Tg(TcrAND)53Hed/J
003147   B10.D2-Hc1 H2d H2-T18c/nSnJ-Tg(DO11.10)10Dlo/J
003199   B10.PL-H2u H2-T18a/(73NS)Sn-Tg(TCRA)B1Jg/J
002116   B6.129S2-Tcratm1Mom/J
005655   B6.Cg-Tg(Tcra,Tcrb)3Ayr/J
008006   B6.Cg-Tg(Tcra51-11.5,Tcrb51-11.5)AR206Ayr/J
005236   B6.Cg-Tg(TcraY1,TcrbY1)416Tev/J
007962   B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J
002115   B6;129S2-Tcratm1Mom/J
004694   B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ
002408   B6;SJL-Tg(TcrAND)53Hed/J
004364   C.Cg-Tcratm1Mom Tcrbtm1Mom/J
003303   C.Cg-Tg(DO11.10)10Dlo/J
006912   C57BL/6-Tg(Tcra2D2,Tcrb2D2)1Kuch/J
003831   C57BL/6-Tg(TcraTcrb)1100Mjb/J
004194   C57BL/6-Tg(TcraTcrb)425Cbn/J
005307   CBy.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005922   CBy.Cg-Thy1a Tg(TcraCl1,TcrbCl1)1Shrm/J
005694   D1Lac.Cg-Tg(Tcra,Tcrb)24Efro/J
004444   NOD.129P2(C)-Tcratm1Mjo/DoiJ
006436   NOD.Cg-(Gpi1-D7Mit346)C57BL/6J Tg(TcraAI4)1Dvs/DvsJ
004257   NOD.Cg-Prkdcscid Tg(TcrLCMV)327Sdz/Dvs
004259   NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
004347   NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs/DvsJ
005686   NOD.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
004696   NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ
004460   NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi/DoiJ
005868   NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ
006303   NOD.FVB-Tg(TcraBDC12-4.1)10Jos/GseJ
004334   NOD/ShiLt-Tg(TcraAI4)1Dvs
003868   NOD/ShiLt-Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
002597   STOCK Tg(TcrHEL3A9)1Mmd/J
View Strains carrying other alleles of Tcra     (34 strains)

Strains carrying other alleles of Tcrb
005308   B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005895   B10.Cg-Thy1a H2d Tg(TcraCl1,TcrbCl1)1Shrm/J
002761   B10.Cg-Tg(TcrAND)53Hed/J
003147   B10.D2-Hc1 H2d H2-T18c/nSnJ-Tg(DO11.10)10Dlo/J
003200   B10.PL-H2u H2-T18a/(73NS)Sn-Tg(TCRB)C14Jg/J
002122   B6.129P2-Tcrbtm1Mom Tcrdtm1Mom/J
002118   B6.129P2-Tcrbtm1Mom/J
005655   B6.Cg-Tg(Tcra,Tcrb)3Ayr/J
008006   B6.Cg-Tg(Tcra51-11.5,Tcrb51-11.5)AR206Ayr/J
005236   B6.Cg-Tg(TcraY1,TcrbY1)416Tev/J
007962   B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J
002121   B6;129P-Tcrbtm1Mom Tcrdtm1Mom/J
002117   B6;129P2-Tcrbtm1Mom/J
004694   B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ
002408   B6;SJL-Tg(TcrAND)53Hed/J
004364   C.Cg-Tcratm1Mom Tcrbtm1Mom/J
003303   C.Cg-Tg(DO11.10)10Dlo/J
006912   C57BL/6-Tg(Tcra2D2,Tcrb2D2)1Kuch/J
003831   C57BL/6-Tg(TcraTcrb)1100Mjb/J
004194   C57BL/6-Tg(TcraTcrb)425Cbn/J
005307   CBy.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005922   CBy.Cg-Thy1a Tg(TcraCl1,TcrbCl1)1Shrm/J
005694   D1Lac.Cg-Tg(Tcra,Tcrb)24Efro/J
006437   NOD.Cg-(Gpi1-D7Mit346)C57BL/6J Tg(TcrbAI4)1Dvs/DvsJ
004257   NOD.Cg-Prkdcscid Tg(TcrLCMV)327Sdz/Dvs
004259   NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
004348   NOD.Cg-Rag1tm1Mom Tg(TcrbAI4)1Dvs/DvsJ
005686   NOD.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
004696   NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ
004460   NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi/DoiJ
005868   NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ
006304   NOD.FVB-Tg(TcrbBDC12-4.1)82Gse/GseJ
003868   NOD/ShiLt-Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
004335   NOD/ShiLt-Tg(TcrbAI4)1Dvs
002597   STOCK Tg(TcrHEL3A9)1Mmd/J
View Strains carrying other alleles of Tcrb     (35 strains)

View Strains carrying other alleles of Thy1     (23 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Animal Health Reports

Room Number           AX12

Research Applications

This mouse can be used to support research in many areas including:

Tcra related

Hematological Research
Immunological Defects

Immunology and Inflammation Research
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects

Research Tools
Cancer Research (specific T cell deficiency)

Tcrb related

Hematological Research
Immunological Defects

Immunology and Inflammation Research
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects

Thy1a related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Research Tools
Genetics Research (Tissue/Cell Markers: T cell specific surface marker)
Immunology and Inflammation Research (T cell specific surface marker)

References

Selected Reference(s)

Overwijk WW; Theoret MR; Finkelstein SE; Surman DR; de Jong LA; Vyth-Dreese FA; Dellemijn TA; Antony PA; Spiess PJ; Palmer DC; Heimann DM; Klebanoff CA; Yu Z; Hwang LN; Feigenbaum L; Kruisbeek AM; Rosenberg SA; Restifo NP. 2003. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med 198(4):569-80. [PubMed: 12925674]  [MGI Ref ID J:85058]

Additional References

Price and Supply Information

Strain Name: B6.Cg-Thy1a/Cy Tg(TcraTcrb)8Rest/J
Stock Number: 005023

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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