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Description
Strain Information
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Edward Rosloniec, Veterans Affairs Medical Center Description
Transgenic mice are viable, fertile, and normal in size. This mutant carries a transgene for a fully functional bovine and mouse type II collagen (260-267) specific IAq-restricted T cell receptor. Flow cytometric analysis show 90% Tcrb-V8.3 expression of CD4+ splenocytes and greater than 95% expression in CD4+ lymphocytes. The transgene confers severe accelerated autoimmune arthritis following type II collagen (CII) immunization. Splenocytes from tolerized mice have altered activation and memory cell surface markers and high levels of Th2 cytokine secretion compared to control. Estradiol completely prevents collagen-induced arthritis (CIA). This mutant mouse may be useful in studies of CIA, rheumatoid arthritis, and T regulatory cells and may also serve as a source of T cells that mediate development of autoimmune diseases.Development
Transgenic constructs containing the mouse alpha and beta chain of the T cell receptor recognizing both bovine and mouse type II collagen (260-267) were cloned from the Tcra-V11.1,Tcra-J(J17) and Tcrb-V8.3,Tcrb-D(D1),Tcrb-J(J1.4) expressing I-Aq-restricted T cell hybridoma qCII85.33. The constructs were co-injected into pronuclei of (C57BL/6 x C3H)F1 eggs. PCR-positive mice (founder line 24) were backcrossed to DBA/1LacJ for 8 generations.
Control Information
| Control | ||
|---|---|---|
| 001140 DBA/1LacJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Tcra
View Strains carrying other alleles of Tcra (35 strains)
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
assigned by genotype
Tg(Tcra,Tcrb)24Efro/0
D1.Cg-Tg(Tcra,Tcrb)24Efro
- immune system phenotype
- abnormal T cell differentiation (MGI Ref ID J:104243)
- following CII-tolerization, transgenic T cells from the spleen show increased levels of activation markers CD69 and CD71, compared to OVA-tolerized transgenic mice eased in CII-tolerized cells
- decreased T cell proliferation (MGI Ref ID J:104243)
- 24 hours after exposure to 200 ug of CII tolerogen, T cells show a greatly reduced capacity to proliferate on CII stimulus compared to T cells from mice exposed to 200 ug of OVA; 48 hours after CII exposure, T cells are refractory to stimulation by CII peptide up to 130 uM
- after 72 hours, CII-tolerized cells can be stimulated by CII concentrations that are >2 logs higher than that needed to stimulate OVA-tolerized transgenic T cells
- suppressed proliferative response is observed up to 7 days post-CII treatment
- increased T cell proliferation (MGI Ref ID J:104243)
- when stimulated in vitro with CII (type II collagen) or a CII peptide, naive T cells show a vigorous proliferative response, while non-transgenic T cells do not
- proliferation of CII-tolerized T cells can be restored when cultured with CII and very high Il2 concentrations
- abnormal cytokine secretion (MGI Ref ID J:104243)
- after overnight CII stimulation, CII-treated T cells produce equivalent levels of Il2 as OVA-treated T cells, but by 48 hours after tolerization, the Il2 response is reduced
- by 48 hours after tolerance induction, production of Th2 cytokines like Il4 and Il10 are enhanced in T cells from CII-treated mice compared to those from OVA-treated mice
- IFNgamma production is elevated in cultures from CII-treated mice
- without CII peptide stimulation, no cytokines can be detected in cultures
- autoimmune response (MGI Ref ID J:104243)
- when immunized with an emulsion containing CII and CFA, mice develop strong T-cell dependent antibody response to the immunogen and the autoantigen, murine CII
- in arthritis incidence in transgenic mice; 100 % of mice tolerized with OVA develop arthritis by day 24 at an accelerated rate, but only 2 mice tolerized with CII develop disease by 42 days
- when mice are tolerized with 3 consecutive doses of 200 ug OVA or CII, no CII-tolerized mice develop arthritis, whereas all OVA-tolerized mice develop disease by day 13
- increased autoantibody level (MGI Ref ID J:104243)
- levels of anti-CII antibody levels are higher than in controls littermates at day 19, but at day 34 levels are high in both groups of mice
- increased susceptibility to autoimmune disorder (MGI Ref ID J:104243)
- immunized mice develop severe accelerated autoimmune arthritis as early as 11 days after immunization with maximum incidence and severity by 35 days compared to non-transgenic littermates which develop arthritis around day 20 and maximum incidence by day 50 which is similar to that seen in wild-type DBA/1 mice
- however, no spontaneous arthritis has been observed in transgenic mice up to 9 months of age
- increased memory T cell number (MGI Ref ID J:104243)
- markers (CD44high and CD62low) for memory T cell phenotypes are increased in CII-tolerized cells
- hematopoietic system phenotype
- abnormal T cell differentiation (MGI Ref ID J:104243)
- following CII-tolerization, transgenic T cells from the spleen show increased levels of activation markers CD69 and CD71, compared to OVA-tolerized transgenic mice eased in CII-tolerized cells
- decreased T cell proliferation (MGI Ref ID J:104243)
- 24 hours after exposure to 200 ug of CII tolerogen, T cells show a greatly reduced capacity to proliferate on CII stimulus compared to T cells from mice exposed to 200 ug of OVA; 48 hours after CII exposure, T cells are refractory to stimulation by CII peptide up to 130 uM
- after 72 hours, CII-tolerized cells can be stimulated by CII concentrations that are >2 logs higher than that needed to stimulate OVA-tolerized transgenic T cells
- suppressed proliferative response is observed up to 7 days post-CII treatment
- increased T cell proliferation (MGI Ref ID J:104243)
- when stimulated in vitro with CII (type II collagen) or a CII peptide, naive T cells show a vigorous proliferative response, while non-transgenic T cells do not
- proliferation of CII-tolerized T cells can be restored when cultured with CII and very high Il2 concentrations
- increased memory T cell number (MGI Ref ID J:104243)
- markers (CD44high and CD62low) for memory T cell phenotypes are increased in CII-tolerized cells
This mouse can be used to support research in many areas including:
Tcra relatedResearch Tools
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
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Tcra,Tcrb)24Efro | ||
|---|---|---|---|
| Allele Name | transgene insertion 24, Edward F Rosloniec | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | qCII24; | ||
| Mutation Made By | Edward Rosloniec, Veterans Affairs Medical Center | ||
| Strain of Origin | (C57BL/6 x C3H)F1 | ||
| Expressed Gene | Tcrb, T-cell receptor beta chain, mouse, laboratory | ||
| Expressed Gene | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Molecular Note | Transgenic constructs containing the mouse alpha and beta chain of the T cell receptor recognizing both bovine and mouse type II collagen (260-267) were cloned from the Tcra-V11.1,Tcra-J(J17) and Tcrb-V8.3,Tcrb-D(D1),Tcrb-J(J1.4) expressing I-Aq-restricted T cell hybridoma qCII85.33. Line 24 was established. The transgenic T cell receptor is expressed on >90% of CD4+ T cells in the spleen and lymph nodes. >90% of alphabeta+ T cells in the thymus. [MGI Ref ID J:104243] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Tcra,Tcrb)24Efro, QPCR, vers. 1
Tg(Tcra)24Efro, STD PCR, vers. 2
Tg(Tcrb)24Efro, STD PCR, vers. 3
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Brand DD; Myers LK; Whittington KB; Latham KA; Stuart JM; Kang AH; Rosloniec EF. 2002. Detection of early changes in autoimmune T cell phenotype and function following intravenous administration of type II collagen in a TCR-transgenic model. J Immunol 168(1):490-8. [PubMed: 11751997] [MGI Ref ID J:104243]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are maintained by breeding transgenic positive littermates.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 001140 DBA/1LacJ | ||
| 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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