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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Generation N?+F1/N?+N1 (11-DEC-07) Donating Investigator Vijay Kuchroo, Brigham and Women's Hospital Description
Mice hemizygous for this "2D2 TCR" (or MOG 35-55 specific TCR) transgene are viable and fertile. The myelin oligodendrocyte glycoprotein (MOG)-specific transgenic T cells are not deleted nor tolerized and are functionally competent. The majority of thymocytes in 2D2 TCR mice express high and intermediate levels of the transgenic T cell receptor (TCR), indicating efficient positive selection of transgenic T cells. The majority of CD4+ splenocytes express the transgenic TCR (as defined by Valpha3.2 and Vbeta11 expression). Cultured splenocytes are responsive to whole myelin oligodendrocyte glycoprotein (MOG) and to MOG 35-55 peptide, but not to ovalbumin (OVA) control peptides. From between 2.5 to 5 months of age, 4% of 2D2 TCR mice develop spontaneous experimental autoimmune encephalomyelitis (EAE), while within the first year 40% of 2D2 TCR mice develop spontaneous, isolated optic neuritis with neither clinical nor histological evidence of EAE. Standard EAE induction protocols produce typical EAE in 2D2 TCR mice, but injection of suboptimal doses of MOG is sufficient to trigger the optic neuritis without stimulating widespread EAE in the central nervous system (CNS). Because the spontaneous diseases observed in 2D2 TCR mice are similar in their incidence and manifestations to those developed by multiple sclerosis (MS) patients, these mice may be useful in immunological studies to investigate the role and nature of the MOG-specific, self-reactive T cell repertoire, as well as to study optic neuritis and its relationship to the development of autoimmunity in the CNS.Development
A myelin oligodendrocyte glycoprotein (MOG) peptide (amino acids 35?55; MEVGWYRSPFSRVVHLYRNGK) was injected into C57BL/6 mice. T lymphocytes from lymph nodes of these immunized mice were isolated and cells expressing the T cell receptor (TCR) combination (Valpha3.2 and Vbeta11) were selected (clone 2D2). The Valpha3.2-Jalpha18 and Vbeta11-DJbeta1.1 sequences of 2D2 TCR were cloned into TCR expression cassettes and the resulting constructs were injected into the pronuclei of fertilized C57BL/6 oocytes. Founder mice were bred with C57BL/6J mice. These 2D2 TCR transgenic mice were bred with wildtype C57BL/6 for many generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Tcra
View Strains carrying other alleles of Tcra (35 strains)
Phenotype
Phenotype Information
assigned by genotype
Tg(Tcra2D2,Tcrb2D2)1Kuch/0
involves: C57BL/6
- life span-post-weaning/aging
- abnormal induced morbidity/mortality (MGI Ref ID J:83278)
- 40% of transgenic mice succumb to EAE compared to no non-transgenic littermates
- nervous system phenotype
- CNS inflammation (MGI Ref ID J:83278)
- 7/15 mice without EAE show typical myelinating/demyelinating lesions of optic neuritis
- mice with EAE show typical myelinating/demyelinating lesions of optic neuritis
- 55 and 78% of transgenic mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions
- abnormal optic nerve morphology (MGI Ref ID J:83278)
- mice with or without EAE that display optic neuritis have myelinating/demyelinating lesions consisting of subpial and endoneurial mononuclear cell infiltrates with demyelination indicated by presence of foamy macrophages
- axon degeneration (MGI Ref ID J:83278)
- mice with optic neuritis have varying degrees of axonal injury and loss
- demyelination (MGI Ref ID J:83278)
- CNS tissues show myelin loss
- vision/eye phenotype
- abnormal eye morphology (MGI Ref ID J:83278)
- superficial eye lesions in mice without EAE are often associated with progressive atrophy of the eye
- 67% of mutants show these eye lesions compared to no wild-type
- abnormal optic nerve morphology (MGI Ref ID J:83278)
- mice with or without EAE that display optic neuritis have myelinating/demyelinating lesions consisting of subpial and endoneurial mononuclear cell infiltrates with demyelination indicated by presence of foamy macrophages
- blepharitis (MGI Ref ID J:83278)
- mice without EAE develop superficial inflammation around the eyelids; this is unilateral and not observed in wild-type littermates during up to 1 year observation
- eyelid edema (MGI Ref ID J:83278)
- mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation
- immune system phenotype
- CNS inflammation (MGI Ref ID J:83278)
- 7/15 mice without EAE show typical myelinating/demyelinating lesions of optic neuritis
- mice with EAE show typical myelinating/demyelinating lesions of optic neuritis
- 55 and 78% of transgenic mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions
- abnormal CD4-positive T cell morphology (MGI Ref ID J:83278)
- CD4/CD8 single positive ratio in thymus of transgenic mice is biased toward CD4+ compartment
- analysis shows a skewing toward CD4+ T cells in spleens as well
- abnormal cytokine secretion (MGI Ref ID J:83278)
- spleen cells from naive mice produce high levels of IFN gamma in response to MOG 35-55
- blepharitis (MGI Ref ID J:83278)
- mice without EAE develop superficial inflammation around the eyelids; this is unilateral and not observed in wild-type littermates during up to 1 year observation
- increased susceptibility to autoimmune disorder (MGI Ref ID J:83278)
- 4% (3/72) of mice develop spontaneous EAE, indicated initially by a limp tail, followed by hindlimb paralysis between 2.5 and 5 months of age
- 55 and 78% of mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions
- mice with disease have typical myelinating/demyelinating lesions
- increased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:83278)
- transgenic mice immunized with MOG 35-55 + pertussis toxin (PT) develop more severe EAE than non-transgenic littermates, with earlier onset and greater clinical scores; 50% of mice develop associated optic neuritis also
- injection of PT alone induces clinical EAE in 39% and histological EAE in 56% of transgenics compared to no non-transgenic mice; 80% of mice develop associated optic neuritis also
- hematopoietic system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:83278)
- CD4/CD8 single positive ratio in thymus of transgenic mice is biased toward CD4+ compartment
- analysis shows a skewing toward CD4+ T cells in spleens as well
- cellular phenotype
- increased cell proliferation (MGI Ref ID J:83278)
- spleen cells from naive mice show increased proliferative response to myelin oligodendrocyte protein peptide 35-55 (MOG 35-55) compared to wild-type mice
- homeostasis/metabolism phenotype
- edema (MGI Ref ID J:83278)
- EAE-affected mice showed edema in the brain and spinal cord
- eyelid edema (MGI Ref ID J:83278)
- mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Tcra2D2,Tcrb2D2)1Kuch/?
involves: C57BL/6 * CD-1
- immune system phenotype
- abnormal interleukin physiology (MGI Ref ID J:125296)
- T cells incubated with LPS-stimulated CD11c+ dendritic cells with IL-23 in the presence of MOG peptide and neutralizing antibodies against IFN-gamma and IL-4 plus either IL-25 or IL-13 antibodies produce less IL-17 than with both IL-25 and IL-13 antibodies or without either
This mouse can be used to support research in many areas including:
Tcra relatedImmunology and Inflammation Research
Autoimmunity (experimental allergic encephalomyelitis (EAE))
Immunodeficiency (multiple immune defects)
Rearranged Antigen-Specific T Cell Receptor Transgenes
Research Tools
Immunology and Inflammation Research (T Cell Receptor Transgenics)
Sensorineural Research
Sensorineural Research
Eye Defects
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
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Tcra2D2,Tcrb2D2)1Kuch | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Vijay Kuchroo | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 2D2; 2D2 TCR; TCRMOG; TCRMOG; | ||
| Mutation Made By | Vijay Kuchroo, Brigham and Women's Hospital | ||
| Expressed Gene | Tcrb, T-cell receptor beta chain, mouse, laboratory | ||
| Expressed Gene | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Molecular Note | The Valpha3.2Jalpha18 region of Tcra from the 2D2 T cell clone as well as the Vbeta11DJbeta1,1 region of Tcrb from the same 2D2 clone were inserted into TCR expression cassettes. The linearized plasmids were injected into the pronuclei of fertilized C57BL/6 oocytes. The 2D2 clone was purified from C57BL/6 mice immunized with a peptide from myelin oligodendrocyte glycoprotein. The amino acid sequence of the CDR3 region from TCR alpha is VYF CALRSY NFG and that from TCR beta is CASS LDCG ANP. [MGI Ref ID J:83278] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Tcra2D2,Tcrb2D2)1Kuch, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Bettelli E; Pagany M; Weiner HL; Linington C; Sobel RA; Kuchroo VK. 2003. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med 197(9):1073-81. [PubMed: 12732654] [MGI Ref ID J:83278]
Additional References
Tg(Tcra2D2,Tcrb2D2)1Kuch relatedAwasthi A; Carrier Y; Peron JP; Bettelli E; Kamanaka M; Flavell RA; Kuchroo VK; Oukka M; Weiner HL. 2007. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8(12):1380-9. [PubMed: 17994022] [MGI Ref ID J:127774]
Bettelli E; Baeten D; Jager A; Sobel RA; Kuchroo VK. 2006. Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice. J Clin Invest 116(9):2393-402. [PubMed: 16955141] [MGI Ref ID J:114666]
Bettelli E; Sullivan B; Szabo SJ; Sobel RA; Glimcher LH; Kuchroo VK. 2004. Loss of T-bet, But Not STAT1, Prevents the Development of Experimental Autoimmune Encephalomyelitis. J Exp Med 200(1):79-87. [PubMed: 15238607] [MGI Ref ID J:91376]
Carl JW Jr; Liu JQ; Joshi PS; El-Omrani HY; Yin L; Zheng X; Whitacre CC; Liu Y; Bai XF. 2008. Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway. J Immunol 181(1):320-8. [PubMed: 18566397] [MGI Ref ID J:137407]
Elyaman W; Kivisakk P; Reddy J; Chitnis T; Raddassi K; Imitola J; Bradshaw E; Kuchroo VK; Yagita H; Sayegh MH; Khoury SJ. 2008. Distinct functions of autoreactive memory and effector CD4+ T cells in experimental autoimmune encephalomyelitis. Am J Pathol 173(2):411-22. [PubMed: 18583313] [MGI Ref ID J:138298]
Frommer F; Heinen TJ; Wunderlich FT; Yogev N; Buch T; Roers A; Bettelli E; Muller W; Anderton SM; Waisman A. 2008. Tolerance without clonal expansion: self-antigen-expressing B cells program self-reactive T cells for future deletion. J Immunol 181(8):5748-59. [PubMed: 18832734] [MGI Ref ID J:140751]
Greve B; Weissert R; Hamdi N; Bettelli E; Sobel RA; Coyle A; Kuchroo VK; Rajewsky K; Schmidt-Supprian M. 2007. I kappa B kinase 2/beta deficiency controls expansion of autoreactive T cells and suppresses experimental autoimmune encephalomyelitis. J Immunol 179(1):179-85. [PubMed: 17579036] [MGI Ref ID J:127765]
Guan Y; Shindler KS; Tabuena P; Rostami AM. 2006. Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice. J Neuroimmunol 178(1-2):40-8. [PubMed: 16828169] [MGI Ref ID J:127769]
Kleinschek MA; Owyang AM; Joyce-Shaikh B; Langrish CL; Chen Y; Gorman DM; Blumenschein WM; McClanahan T; Brombacher F; Hurst SD; Kastelein RA; Cua DJ. 2007. IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med 204(1):161-70. [PubMed: 17200411] [MGI Ref ID J:125296]
Korn T; Reddy J; Gao W; Bettelli E; Awasthi A; Petersen TR; Backstrom BT; Sobel RA; Wucherpfennig KW; Strom TB; Oukka M; Kuchroo VK. 2007. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13(4):423-31. [PubMed: 17384649] [MGI Ref ID J:127766]
Krishnamoorthy G; Lassmann H; Wekerle H; Holz A. 2006. Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Invest 116(9):2385-92. [PubMed: 16955140] [MGI Ref ID J:114667]
Laouar Y; Town T; Jeng D; Tran E; Wan Y; Kuchroo VK; Flavell RA. 2008. TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 105(31):10865-70. [PubMed: 18669656] [MGI Ref ID J:140054]
Lu L; Ikizawa K; Hu D; Werneck MB; Wucherpfennig KW; Cantor H. 2007. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity 26(5):593-604. [PubMed: 17509909] [MGI Ref ID J:123555]
Petersen TR; Gulland S; Bettelli E; Kuchroo V; Palmer E; Backstrom BT. 2004. A chimeric T cell receptor with super-signaling properties. Int Immunol 16(7):889-94. [PubMed: 15148288] [MGI Ref ID J:125963]
Petersen TR; Lata R; Spittle E; Backstrom BT. 2007. A chimeric TCR-beta chain confers increased susceptibility to EAE. Mol Immunol 44(14):3473-81. [PubMed: 17481734] [MGI Ref ID J:125962]
Quintana FJ; Basso AS; Iglesias AH; Korn T; Farez MF; Bettelli E; Caccamo M; Oukka M; Weiner HL. 2008. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453(7191):65-71. [PubMed: 18362915] [MGI Ref ID J:136052]
Shinohara ML; Kim JH; Garcia VA; Cantor H. 2008. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 29(1):68-78. [PubMed: 18619869] [MGI Ref ID J:137879]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice are bred to wildtype siblings or to inbred C57BL/6J (Stock No. 000664). Mating System +/+ sibling x Hemizygote (Female x Male) 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* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Hemizygous for Tg(Tcra2D2,Tcrb2D2)1Kuch *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Hemizygous for Tg(Tcra2D2,Tcrb2D2)1Kuch x Noncarrier $288.65 Noncarrier x Hemizygous for Tg(Tcra2D2,Tcrb2D2)1Kuch
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Hemizygous for Tg(Tcra2D2,Tcrb2D2)1Kuch *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Hemizygous for Tg(Tcra2D2,Tcrb2D2)1Kuch x Noncarrier $375.30 Noncarrier x Hemizygous for Tg(Tcra2D2,Tcrb2D2)1Kuch
Additional Supply Details
| Supply Notes |
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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 ~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 Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| 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. | ||
General Terms and Conditions
See Terms of Use
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| fax: | 207-288-6655 |
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