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Description
Strain Information
Former Names 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 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Species laboratory mouse Generation N?+N1F11 (30-DEC-08) Donating Investigator Nicholas Restifo, National Cancer Institute 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.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.
Control Information
| Control | ||
|---|---|---|
| 000406 B6.PL-Thy1a/CyJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Thy1a allele
005895 B10.Cg-Thy1a H2d Tg(TcraCl1,TcrbCl1)1Shrm/J 001317 B6.Cg-Igha Thy1a Gpi1a/J 000406 B6.PL-Thy1a/CyJ 000983 B6.PL/(84NS)CyJ 007687 BKa.Cg-Sox17tm1Sjm Ptprcb Thy1a/J 007686 BKa.Cg-Sox17tm2Sjm Ptprcb Thy1a/J 005307 CBy.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ 005922 CBy.Cg-Thy1a Tg(TcraCl1,TcrbCl1)1Shrm/J 005443 CBy.PL(B6)-Thy1a/ScrJ 005686 NOD.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ 004483 NOD.NON-Thy1a/1LtJ 002721 NOD.NON-Thy1a/J 005651 SJL.AK-Thy1a/TseJ 003961 SJL.Cg Thy1a-Noxo1hslt/J View Strains carrying Thy1a (14 strains)
Additional Web Information
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
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 (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
This mouse can be used to support research in many areas including:Tcra related
Tcrb relatedHematological Research
Immunological Defects
Immunology and Inflammation Research
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects
Research Tools
Cancer Research
specific T cell deficiency
Thy1a relatedHematological Research
Immunological Defects
Immunology and Inflammation Research
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects
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
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(TcraTcrb)8Rest | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Nicholas Restifo | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Pmel-1; Pmel-I; | ||
| Mutation Made By | Marc Theoret, NIH | ||
| Strain of Origin | C57BL/6 | ||
| Expressed Gene | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Expressed Gene | Tcrb, T-cell receptor beta 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 | ||
| Allele Type | Not Applicable | ||
| Common Name(s) | Thy-1.1; Thy1.1; Thy1a; theta-AKR; thetaAKR; | ||
| 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; theta; | ||
| 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 isthe same size as Thy1 and is expressed on thymus and brain but not on lymph node and spleen cells (J:7900). | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(TcraTcrb)8Rest, QPCR
Helpful Links
Genotyping resources and troubleshooting
References
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
Antony PA; Paulos CM; Ahmadzadeh M; Akpinarli A; Palmer DC; Sato N; Kaiser A; Hinrichs CS; Klebanoff CA; Tagaya Y; Restifo NP. 2006. Interleukin-2-dependent mechanisms of tolerance and immunity in vivo. J Immunol 176(9):5255-66. [PubMed: 16621991] [MGI Ref ID J:115150]
Klebanoff CA; Finkelstein SE; Surman DR; Lichtman MK; Gattinoni L; Theoret MR; Grewal N; Spiess PJ; Antony PA; Palmer DC; Tagaya Y; Rosenberg SA; Waldmann TA; Restifo NP. 2004. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci U S A 101(7):1969-74. [PubMed: 14762166] [MGI Ref ID J:90388]
Thy1a relatedTg(TcraTcrb)8Rest relatedBeck PL; Li Y; Wong J; Chen CW; Keenan CM; Sharkey KA; McCafferty DM. 2007. Inducible nitric oxide synthase from bone marrow-derived cells plays a critical role in regulating colonic inflammation. Gastroenterology 132(5):1778-90. [PubMed: 17449036] [MGI Ref ID J:128325]
Chen TT; Li L; Chung DH; Allen CD; Torti SV; Torti FM; Cyster JG; Chen CY; Brodsky FM; Niemi EC; Nakamura MC; Seaman WE; Daws MR. 2005. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med 202(7):955-65. [PubMed: 16203866] [MGI Ref ID J:107466]
D'Eustachio P; Owens GC; Edelman GM; Cunningham BA. 1985. Chromosomal location of the gene encoding the neural cell adhesion molecule (N-CAM) in the mouse. Proc Natl Acad Sci U S A 82(22):7631-5. [PubMed: 3865183] [MGI Ref ID J:8111]
Fife BT; Griffin MD; Abbas AK; Locksley RM; Bluestone JA. 2006. Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist. J Clin Invest 116(8):2252-61. [PubMed: 16886063] [MGI Ref ID J:113109]
Green MC; Sweet HO. 1975. [Hx - Hm - W.] Mouse News Lett 52:38. [MGI Ref ID J:13675]
Leiter EH. 1998. NOD Mice and Related Strains: Origins, Husbandry and Biology Introduction. In: NOD Mice and Related Strains: Research Applications in Diabetes, AIDS, Cancer, and Other Diseases. RG Landes, Austin. [MGI Ref ID J:110093]
REIF AE; ALLEN JM. 1964. THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES. J Exp Med 120:413-33. [PubMed: 14207060] [MGI Ref ID J:24839]
Ranheim EA; Tarbell KV; Krogsgaard M; Mallet-Designe V; Teyton L; McDevitt HO; Weissman IL. 2004. Selection of aberrant class II restricted CD8+ T cells in NOD mice expressing a glutamic acid decarboxylase (GAD)65-specific T cell receptor transgene. Autoimmunity 37(8):555-67. [PubMed: 15763918] [MGI Ref ID J:128250]
Read S; Hogan TV; Zwar TD; Gleeson PA; Van Driel IR. 2007. Prevention of autoimmune gastritis in mice requires extra-thymic T-cell deletion and suppression by regulatory T cells. Gastroenterology 133(2):547-58. [PubMed: 17603058] [MGI Ref ID J:128303]
Reif AE; Allen JM. 1966. Mouse thymic iso-antigens. Nature 209(22):521-3. [PubMed: 5919593] [MGI Ref ID J:5012]
Voehringer D; Liang HE; Locksley RM. 2008. Homeostasis and effector function of lymphopenia-induced 'memory-like' T cells in constitutively T cell-depleted mice. J Immunol 180(7):4742-53. [PubMed: 18354198] [MGI Ref ID J:133382]
Wuthrich M; Warner T; Klein BS. 2005. IL-12 is required for induction but not maintenance of protective, memory responses to Blastomyces dermatitidis: implications for vaccine development in immune-deficient hosts. J Immunol 175(8):5288-97. [PubMed: 16210634] [MGI Ref ID J:119110]
Xiao Z; Mescher MF; Jameson SC. 2007. Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation. J Exp Med 204(11):2667-77. [PubMed: 17954566] [MGI Ref ID J:126126]
Zaleski M; Klein J. 1974. Immune response of mice to Thy-1. 1 antigen: genetic control by alleles at the Ir-5 locus loosely linked to the H-2 complex. J Immunol 113(4):1170-7. [PubMed: 4606643] [MGI Ref ID J:5487]
Zaleski MB. 1975. Immune response of mice to the Thy-1.1 antigen: effect of the Ir-5 alleles studies in 129/J and B10.129(6M) mice Immunogenetics 2:241-8. [MGI Ref ID J:30773]
Antony PA; Paulos CM; Ahmadzadeh M; Akpinarli A; Palmer DC; Sato N; Kaiser A; Hinrichs CS; Klebanoff CA; Tagaya Y; Restifo NP. 2006. Interleukin-2-dependent mechanisms of tolerance and immunity in vivo. J Immunol 176(9):5255-66. [PubMed: 16621991] [MGI Ref ID J:115150]
Antony PA; Piccirillo CA; Akpinarli A; Finkelstein SE; Speiss PJ; Surman DR; Palmer DC; Chan CC; Klebanoff CA; Overwijk WW; Rosenberg SA; Restifo NP. 2005. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 174(5):2591-601. [PubMed: 15728465] [MGI Ref ID J:129825]
Barbee SD; Alberola-Ila J. 2006. Phosphatidylinositol 3-kinase improves the efficiency of positive selection. Int Immunol 18(6):921-30. [PubMed: 16636016] [MGI Ref ID J:109137]
Fujita M; Zhu X; Ueda R; Sasaki K; Kohanbash G; Kastenhuber ER; McDonald HA; Gibson GA; Watkins SC; Muthuswamy R; Kalinski P; Okada H. 2009. Effective immunotherapy against murine gliomas using type 1 polarizing dendritic cells--significant roles of CXCL10. Cancer Res 69(4):1587-95. [PubMed: 19190335] [MGI Ref ID J:146507]
Gattinoni L; Ranganathan A; Surman DR; Palmer DC; Antony PA; Theoret MR; Heimann DM; Rosenberg SA; Restifo NP. 2006. CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent. Blood 108(12):3818-23. [PubMed: 16882704] [MGI Ref ID J:140448]
Gattinoni L; Zhong XS; Palmer DC; Ji Y; Hinrichs CS; Yu Z; Wrzesinski C; Boni A; Cassard L; Garvin LM; Paulos CM; Muranski P; Restifo NP. 2009. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 15(7):808-13. [PubMed: 19525962] [MGI Ref ID J:151525]
Hinrichs CS; Borman ZA; Cassard L; Gattinoni L; Spolski R; Yu Z; Sanchez-Perez L; Muranski P; Kern SJ; Logun C; Palmer DC; Ji Y; Reger RN; Leonard WJ; Danner RL; Rosenberg SA; Restifo NP. 2009. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci U S A 106(41):17469-74. [PubMed: 19805141] [MGI Ref ID J:153682]
Hinrichs CS; Kaiser A; Paulos CM; Cassard L; Sanchez-Perez L; Heemskerk B; Wrzesinski C; Borman ZA; Muranski P; Restifo NP. 2009. Type 17 CD8+ T cells display enhanced antitumor immunity. Blood 114(3):596-9. [PubMed: 19471017] [MGI Ref ID J:150734]
Hinrichs CS; Spolski R; Paulos CM; Gattinoni L; Kerstann KW; Palmer DC; Klebanoff CA; Rosenberg SA; Leonard WJ; Restifo NP. 2008. IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 111(11):5326-33. [PubMed: 18276844] [MGI Ref ID J:135563]
Keller AM; Schildknecht A; Xiao Y; van den Broek M; Borst J. 2008. Expression of costimulatory ligand CD70 on steady-state dendritic cells breaks CD8+ T cell tolerance and permits effective immunity. Immunity 29(6):934-46. [PubMed: 19062317] [MGI Ref ID J:142683]
Klebanoff CA; Finkelstein SE; Surman DR; Lichtman MK; Gattinoni L; Theoret MR; Grewal N; Spiess PJ; Antony PA; Palmer DC; Tagaya Y; Rosenberg SA; Waldmann TA; Restifo NP. 2004. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci U S A 101(7):1969-74. [PubMed: 14762166] [MGI Ref ID J:90388]
Kohlmeyer J; Cron M; Landsberg J; Bald T; Renn M; Mikus S; Bondong S; Wikasari D; Gaffal E; Hartmann G; Tuting T. 2009. Complete regression of advanced primary and metastatic mouse melanomas following combination chemoimmunotherapy. Cancer Res 69(15):6265-74. [PubMed: 19622767] [MGI Ref ID J:150944]
Leithauser F; Meinhardt-Krajina T; Fink K; Wotschke B; Moller P; Reimann J. 2006. Foxp3-expressing CD103+ regulatory T cells accumulate in dendritic cell aggregates of the colonic mucosa in murine transfer colitis. Am J Pathol 168(6):1898-909. [PubMed: 16723705] [MGI Ref ID J:109127]
Quezada SA; Peggs KS; Simpson TR; Shen Y; Littman DR; Allison JP. 2008. Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. J Exp Med 205(9):2125-38. [PubMed: 18725522] [MGI Ref ID J:138811]
Rizzuto GA; Merghoub T; Hirschhorn-Cymerman D; Liu C; Lesokhin AM; Sahawneh D; Zhong H; Panageas KS; Perales MA; Altan-Bonnet G; Wolchok JD; Houghton AN. 2009. Self-antigen-specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response. J Exp Med 206(4):849-66. [PubMed: 19332877] [MGI Ref ID J:147866]
Shu CJ; Radu CG; Shelly SM; Vo DD; Prins R; Ribas A; Phelps ME; Witte ON. 2009. Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen. Int Immunol 21(2):155-65. [PubMed: 19106231] [MGI Ref ID J:144521]
Yi H; Yu X; Gao P; Wang Y; Baek SH; Chen X; Kim HL; Subjeck JR; Wang XY. 2009. Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation. Blood 113(23):5819-28. [PubMed: 19349620] [MGI Ref ID J:149497]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Homozygous for Thy1a, Homozygous for Tg(TcraTcrb)8Rest
Pairs /Price (US dollars $) Pair Genotype $487.00 Homozygous for Thy1a, Homozygous for Tg(TcraTcrb)8Rest x Homozygous for Thy1a, Homozygous for Tg(TcraTcrb)8Rest
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Homozygous for Thy1a, Homozygous for Tg(TcraTcrb)8Rest
Pairs /Price (US dollars $) Pair Genotype $633.10 Homozygous for Thy1a, Homozygous for Tg(TcraTcrb)8Rest x Homozygous for Thy1a, Homozygous for Tg(TcraTcrb)8Rest
Additional Supply Details
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Supply Details
| Standard Supply | Repository-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 approximately 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 two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000406 B6.PL-Thy1a/CyJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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