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Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse H2 Haplotype g7 Generation [?+F2N1p]+F5N1F1 (23-JAN-08) Donating Investigator David Serreze, The Jackson Laboratory Appearance
pink-eyed, albino
Related Genotype: A/A Tyrc/TyrcDescription
NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ, commonly called 8.3-NOD, express rearranged Tcra and Tcrb transgenes derived from the pancreatic beta cell-cytotoxic CD8+ T cell clone NY8.3. CD4-CD8+ thymocytes and lymph derived T cells are skewed toward VB8.1/2+ expression when compared to wild type controls. Although, transgenic mice exhibit dramatically accelerated diabetes, the cumulative diabetes incidence and kinetics of disease are remarkably similar to their wild type cohorts. Insulitis scores of 3 week old transgene+ mice was significantly lower, while insulitis scores of 6 week olds were significantly more severe than in wild types controls, Verdaguer J et al, 1997, J. Exp Med 186, 1663-1676.
Transgenic animals bearing both TCR transgenes offer a source of CTL precursors useful in examining the diversity of beta cell peptides recognized by the autoreactive CD8+ T lymphocytes contributing to the earliest phase of IDDM development.Development
(SJLXC57BL/6J)F2 transgenic mice were backcrossed to NOD. In 2005, the Type 1 Diabetes Resource received congenic NOD hemizygous transgenic mice backcrossed at least 14 generations to NOD.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Tcra
View Strains carrying other alleles of Tcra (35 strains)
Strains carrying other alleles of Tcrb
View Strains carrying other alleles of Tcrb (39 strains)
Congenic Nomenclature
View Related Disease (OMIM) Terms
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(TcraTcrbNY8.3)1Pesa/?
involves: C57BL/6 * NOD * SJL
- immune system phenotype
- pancreas inflammation (MGI Ref ID J:44202)
- insulitis at 3 weeks less than in controls
- insulitis at 6 weeks of age significantly greater than in controls
- homeostasis/metabolism phenotype
- increased circulating glucose level (MGI Ref ID J:44202)
- diabetes develops in 26% (males) to 33% (females) of mice
- diabetes slow to develop and moderate
- endocrine/exocrine gland phenotype
- pancreas inflammation (MGI Ref ID J:44202)
- insulitis at 3 weeks less than in controls
- insulitis at 6 weeks of age significantly greater than in controls
- digestive/alimentary phenotype
- pancreas inflammation (MGI Ref ID J:44202)
- insulitis at 3 weeks less than in controls
- insulitis at 6 weeks of age significantly greater than in controls
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Tcra relatedImmunology and Inflammation Research
Rearranged Antigen-Specific T Cell Receptor Transgenes
Research Tools
Diabetes and Obesity Research
Immunology and Inflammation Research (T Cell Receptor Transgenics)
Tcrb relatedHematological Research
Immunological Defects
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects
Research Tools
Cancer Research (specific T cell deficiency)
Hematological Research
Immunological Defects
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects
| Allele Symbol | Tg(TcraTcrbNY8.3)1Pesa | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Pere Santamaria | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 8.3-TCR; 8.3-TCR-TG; 8.3-TCR-alpha/beta transgene; 8.3TCR; NY8.3; Tcr8.3; | ||
| Mutation Made By | Pere Santamaria, University of Calgary | ||
| Strain of Origin | (SJL x C57BL/6)F2 | ||
| Expressed Gene | Tcrb, T-cell receptor beta chain, mouse, laboratory | ||
| Expressed Gene | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Molecular Note | Functional VDJbeta and VJalpha rearrangements were isolated from the beta cell cytotoxic CD8(+) T cell clone NY8.3. Upstream regualtory sequence together with either TCR-beta enhancers or TCR-alpha enhancers, as appropriate, were associated with VDJbetaor VJalpha. [MGI Ref ID J:44202] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
Verdaguer J; Schmidt D; Amrani A; Anderson B; Averill N; Santamaria P. 1997. Spontaneous autoimmune diabetes in monoclonal T cell nonobese diabetic mice. J Exp Med 186(10):1663-76. [PubMed: 9362527] [MGI Ref ID J:44202]
Tg(TcraTcrbNY8.3)1Pesa relatedAmrani A; Serra P; Yamanouchi J; Han B; Thiessen S; Verdaguer J; Santamaria P. 2002. CD154-dependent priming of diabetogenic CD4(+) T cells dissociated from activation of antigen-presenting cells. Immunity 16(5):719-32. [PubMed: 12049723] [MGI Ref ID J:76802]
Amrani A; Verdaguer J; Anderson B; Utsugi T; Bou S; Santamaria P. 1999. Perforin-independent beta-cell destruction by diabetogenic CD8(+) T lymphocytes in transgenic nonobese diabetic mice. J Clin Invest 103(8):1201-9. [PubMed: 10207172] [MGI Ref ID J:108737]
Chong MM; Chen Y; Darwiche R; Dudek NL; Irawaty W; Santamaria P; Allison J; Kay TW; Thomas HE. 2004. Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction. J Immunol 172(9):5714-21. [PubMed: 15100317] [MGI Ref ID J:89692]
DiLorenzo TP; Lieberman SM; Takaki T; Honda S; Chapman HD; Santamaria P; Serreze DV; Nathenson SG. 2002. During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities. Clin Immunol 105(3):332-41. [PubMed: 12498815] [MGI Ref ID J:94192]
Dudek NL; Thomas HE; Mariana L; Sutherland RM; Allison J; Estella E; Angstetra E; Trapani JA; Santamaria P; Lew AM; Kay TW. 2006. Cytotoxic T-cells from T-cell receptor transgenic NOD8.3 mice destroy beta-cells via the perforin and Fas pathways. Diabetes 55(9):2412-8. [PubMed: 16936188] [MGI Ref ID J:116592]
Fallarino F; Grohmann U; You S; McGrath BC; Cavener DR; Vacca C; Orabona C; Bianchi R; Belladonna ML; Volpi C; Santamaria P; Fioretti MC; Puccetti P. 2006. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176(11):6752-61. [PubMed: 16709834] [MGI Ref ID J:131797]
Graham KL; Sanders N; Tan Y; Allison J; Kay TW; Coulson BS. 2008. Rotavirus infection accelerates type 1 diabetes in mice with established insulitis. J Virol 82(13):6139-49. [PubMed: 18417562] [MGI Ref ID J:138082]
Han B; Serra P; Yamanouchi J; Amrani A; Elliott JF; Dickie P; Dilorenzo TP; Santamaria P. 2005. Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes. J Clin Invest 115(7):1879-87. [PubMed: 15937548] [MGI Ref ID J:99646]
Judkowski V; Krakowski M; Rodriguez E; Mocnick L; Santamaria P; Sarvetnick N. 2004. Increased islet antigen presentation leads to type-1 diabetes in mice with autoimmune susceptibility. Eur J Immunol 34(4):1031-40. [PubMed: 15048713] [MGI Ref ID J:88883]
Krishnamurthy B; Dudek NL; McKenzie MD; Purcell AW; Brooks AG; Gellert S; Colman PG; Harrison LC; Lew AM; Thomas HE; Kay TW. 2006. Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. J Clin Invest 116(12):3258-65. [PubMed: 17143333] [MGI Ref ID J:117352]
Krishnamurthy B; Mariana L; Gellert SA; Colman PG; Harrison LC; Lew AM; Santamaria P; Thomas HE; Kay TW. 2008. Autoimmunity to Both Proinsulin and IGRP Is Required for Diabetes in Nonobese Diabetic 8.3 TCR Transgenic Mice. J Immunol 180(7):4458-4464. [PubMed: 18354167] [MGI Ref ID J:132969]
Leiter EH; Reifsnyder P; Driver J; Kamdar S; Choisy-Rossi C; Serreze DV; Hara M; Chervonsky A. 2007. Unexpected functional consequences of xenogeneic transgene expression in beta-cells of NOD mice. Diabetes Obes Metab 9 Suppl 2:14-22. [PubMed: 17919174] [MGI Ref ID J:127015]
Serra P; Amrani A; Yamanouchi J; Han B; Thiessen S; Utsugi T; Verdaguer J; Santamaria P. 2003. CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells. Immunity 19(6):877-89. [PubMed: 14670304] [MGI Ref ID J:86995]
Thomas HE; Irawaty W; Darwiche R; Brodnicki TC; Santamaria P; Allison J; Kay TW. 2004. IL-1 Receptor Deficiency Slows Progression to Diabetes in the NOD Mouse. Diabetes 53(1):113-121. [PubMed: 14693705] [MGI Ref ID J:87251]
Ueno A; Cho S; Cheng L; Wang J; Hou S; Nakano H; Santamaria P; Yang Y. 2007. Transient upregulation of indoleamine 2,3-dioxygenase in dendritic cells by human chorionic gonadotropin downregulates autoimmune diabetes. Diabetes 56(6):1686-93. [PubMed: 17360980] [MGI Ref ID J:126514]
Verdaguer J; Amrani A; Anderson B; Schmidt D; Santamaria P. 1999. Two mechanisms for the non-MHC-linked resistance to spontaneous autoimmunity. J Immunol 162(8):4614-26. [PubMed: 10202001] [MGI Ref ID J:109898]
Wang J; Cho S; Ueno A; Cheng L; Xu BY; Desrosiers MD; Shi Y; Yang Y. 2008. Ligand-dependent induction of noninflammatory dendritic cells by anergic invariant NKT cells minimizes autoimmune inflammation. J Immunol 181(4):2438-45. [PubMed: 18684934] [MGI Ref ID J:140188]
Yamanouchi J; Rainbow D; Serra P; Howlett S; Hunter K; Garner VE; Gonzalez-Munoz A; Clark J; Veijola R; Cubbon R; Chen SL; Rosa R; Cumiskey AM; Serreze DV; Gregory S; Rogers J; Lyons PA; Healy B; Smink LJ; Todd JA; Peterson LB; Wicker LS; Santamaria P. 2007. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet 39(3):329-37. [PubMed: 17277778] [MGI Ref ID J:120349]
Zwicker KA; Gratton KJ; Santamaria P; Bathe OF. 2003. Tumor immunity in the context of autoimmunity. J Surg Res 114(2):274. [PubMed: 14559559] [MGI Ref ID J:86058]
de Jersey J; Snelgrove SL; Palmer SE; Teteris SA; Mullbacher A; Miller JF; Slattery RM. 2007. Beta cells cannot directly prime diabetogenic CD8 T cells in nonobese diabetic mice. Proc Natl Acad Sci U S A 104(4):1295-300. [PubMed: 17229843] [MGI Ref ID J:119514]
Animal Health Reports
Room Number FGB29
Colony Maintenance
Breeding & Husbandry FACS analysis, utlizing VB8.1,2,3 FITC antibody costaining with CD8a PE, is used to genotype mice from this strain. The accelerated diabetes development in NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ hemizygous breeding stock is not significantly retarded by Complete Freund's Adjuvant.
Mating System +/+ sibling x Hemizygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $54.00 Female or Male Hemizygous for Tg(TcraTcrbNY8.3)1Pesa *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $108.00 Hemizygous for Tg(TcraTcrbNY8.3)1Pesa x Hemizygous for Tg(TcraTcrbNY8.3)1Pesa
| Supply Notes |
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| Pricing for International shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $70.20 Female or Male Hemizygous for Tg(TcraTcrbNY8.3)1Pesa *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $140.40 Hemizygous for Tg(TcraTcrbNY8.3)1Pesa x Hemizygous for Tg(TcraTcrbNY8.3)1Pesa
| Supply Notes |
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|---|
| 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 ~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. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | (approximate) | |
| 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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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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