| |||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names STOCK Tg(TcrHEL3A9)Mmd/J (Changed: 16-MAY-08 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Generation N4F?+9p Donating Investigator Mark Davis, Stanford University School of Medicine Appearance
black
Related Genotype: a/aDescription
Mice carrying the (TcrHEL3A9) transgene express the alpha and beta chains of a T-cell receptor specific for hen egg lysozyme. Transgenics are used to study maintenance and breakdown of immunological tolerance, overcoming of the anergic state, and issues of costimuli.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 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
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(TcrHEL3A9)1Mmd/0
involves: C57BL/6
- immune system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:73608)
- vast majority of CD4 T cells express a T cell receptor that is specific for hen egg lysozyme (HEL) antigen
- abnormal T cell activation (MGI Ref ID J:73608)
- CD4 T cells become activated when cultured with HEL protein and B cells from Tg(IghelMD4)4Ccg transgenic mice
- 12 hours of culture leads to upregulation of CD69 on the cell surface
- CD4 T cells enlarge into blasts and express high levels of CD44 after 48 hours in culture
- supernatant from these cultures supports a IL-2/IL-4 dependent cell line
- the use of HEL peptide leads to similar but somewhat reduced levels of activation
- increased T cell proliferation (MGI Ref ID J:73608)
- abnormal interleukin secretion (MGI Ref ID J:73608)
- CD4 T cells become activated and secrete cytokines when cultured with HEL protein and B cells from Tg(IghelMD4)4Ccg transgenic mice
- supernatant from these cultures supports a IL-2/IL-4 dependent cell line
- hematopoietic system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:73608)
- vast majority of CD4 T cells express a T cell receptor that is specific for hen egg lysozyme (HEL) antigen
- abnormal T cell activation (MGI Ref ID J:73608)
- CD4 T cells become activated when cultured with HEL protein and B cells from Tg(IghelMD4)4Ccg transgenic mice
- 12 hours of culture leads to upregulation of CD69 on the cell surface
- CD4 T cells enlarge into blasts and express high levels of CD44 after 48 hours in culture
- supernatant from these cultures supports a IL-2/IL-4 dependent cell line
- the use of HEL peptide leads to similar but somewhat reduced levels of activation
- increased T cell proliferation (MGI Ref ID J:73608)
Tg(TcrHEL3A9)1Mmd/0
involves: C57BL/6 * C57BL/10 * C57BR/cd
- immune system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:78309)
- 15% of total lymphocytes found in lymph nodes are CD4 T cells bearing the transgenic TCR
- CD4 T cells that express the transgenic TCR-beta chain also express low or high amounts of the TCR-alpha chain
- the CD4 T cells expressing the low amounts of transgenic TCR-alpha may also express endogenous TCR-alpha chains
- decreased CD4-positive T cell number (MGI Ref ID J:78309)
- CD 4 T cell numbers in the lymph nodes are reduced by about a third
- abnormal T cell activation (MGI Ref ID J:78309)
- in vitro TCR stimulation leads to reduced expression of CD69 compared to T cells from mice transgenic for just the TCR
- abnormal T cell proliferation (MGI Ref ID J:78309)
- CD4 T cells expressing the transgenic TCR proliferate in response to hen egg lysozyme
- proliferation occurs whether CD4 T cells are low or high expressers of the transgenic TCR-alpha chain
- abnormal double-positive T cell morphology (MGI Ref ID J:78309)
- 55.9% of the double-positive thymocytes express the transgenic TCR
- abnormal thymus cell ratio (MGI Ref ID J:78309)
- there is a skewing towards the CD-4 T cell subset in mice on a homozygote H2k/k background
- the ratio of T cell subsets in the thymus is skewed toward CD8 T cells on a heterozygote H2b/k background
- hematopoietic system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:78309)
- 15% of total lymphocytes found in lymph nodes are CD4 T cells bearing the transgenic TCR
- CD4 T cells that express the transgenic TCR-beta chain also express low or high amounts of the TCR-alpha chain
- the CD4 T cells expressing the low amounts of transgenic TCR-alpha may also express endogenous TCR-alpha chains
- decreased CD4-positive T cell number (MGI Ref ID J:78309)
- CD 4 T cell numbers in the lymph nodes are reduced by about a third
- abnormal T cell activation (MGI Ref ID J:78309)
- in vitro TCR stimulation leads to reduced expression of CD69 compared to T cells from mice transgenic for just the TCR
- abnormal T cell proliferation (MGI Ref ID J:78309)
- CD4 T cells expressing the transgenic TCR proliferate in response to hen egg lysozyme
- proliferation occurs whether CD4 T cells are low or high expressers of the transgenic TCR-alpha chain
- abnormal double-positive T cell morphology (MGI Ref ID J:78309)
- 55.9% of the double-positive thymocytes express the transgenic TCR
- abnormal thymus cell ratio (MGI Ref ID J:78309)
- there is a skewing towards the CD-4 T cell subset in mice on a homozygote H2k/k background
- the ratio of T cell subsets in the thymus is skewed toward CD8 T cells on a heterozygote H2b/k background
This mouse can be used to support research in many areas including:
Tcra relatedImmunology and Inflammation Research
Rearranged Antigen-Specific T Cell Receptor Transgenes (class II restricted)
Research 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(TcrHEL3A9)1Mmd | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Mark M Davis | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 3A9 TCR; 3A9 anti-HEL; Tg(TcrHEL3A9)Mmd; | ||
| Strain of Origin | C57BL/6J | ||
| Expressed Gene | Tcrb, T-cell receptor beta chain, mouse, laboratory | ||
| Expressed Gene | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Promoter | Tcrb, T-cell receptor beta chain, mouse, laboratory | ||
| Promoter | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Molecular Note | Transgenic mice produced from this construct carry transgenes encoding the T cell receptor alpha and beta (Tcra and Tcrb, respectively) chains from the hen egg lysozyme (HEL)-specific T cell hybridoma 3A9. Two vectors were constructed and subsequently co-injected into C57BL/6J eggs. The first vector contained the Tcra variable and joining regions (V and J, respectively) and a 3.5kb segment 3' to the Tcra constant region. The second vector contained the Tcrb variable, diversity, and joining regions (V, D, and J, respectively) and a 7.5kb segment 3' to the Tcrb constant region, which included the Tcrb enhancer region. Transgenic mice expressed the alpha and beta chains of a T cell receptor specific for hen egg lysozyme. Two female founders were generated. [MGI Ref ID J:73608] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(TcrHEL3A9)1Mmd, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Ho WY; Cooke MP; Goodnow CC; Davis MM. 1994. Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells. J Exp Med 179(5):1539-49. [PubMed: 7909325] [MGI Ref ID J:73608]
Additional References
Tg(TcrHEL3A9)1Mmd relatedAkkaraju S; Ho WY; Leong D; Canaan K; Davis MM; Goodnow CC. 1997. A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis. Immunity 7(2):255-71. [PubMed: 9285410] [MGI Ref ID J:78309]
DiPaolo RJ; Unanue ER. 2001. The level of peptide-MHC complex determines the susceptibility to autoimmune diabetes: studies in HEL transgenic mice. Eur J Immunol 31(12):3453-9. [PubMed: 11745364] [MGI Ref ID J:73354]
Fournier S; Rathmell JC; Goodnow CC; Allison JP. 1997. T cell-mediated elimination of B7.2 transgenic B cells. Immunity 6(3):327-39. [PubMed: 9075933] [MGI Ref ID J:112475]
Gosling KM; Makaroff LE; Theodoratos A; Kim YH; Whittle B; Rui L; Wu H; Hong NA; Kennedy GC; Fritz JA; Yates AL; Goodnow CC; Fahrer AM. 2007. A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development. Proc Natl Acad Sci U S A 104(30):12445-50. [PubMed: 17640884] [MGI Ref ID J:123300]
Hailman E; Allen PM. 2005. Inefficient cell spreading and cytoskeletal polarization by CD4+CD8+ thymocytes: regulation by the thymic environment. J Immunol 175(8):4847-57. [PubMed: 16210586] [MGI Ref ID J:119055]
Ham DI; Kim SJ; Chen J; Vistica BP; Fariss RN; Lee RS; Wawrousek EF; Takase H; Yu CR; Egwuagu CE; Chan CC; Gery I. 2004. Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter. Invest Ophthalmol Vis Sci 45(3):857-62. [PubMed: 14985302] [MGI Ref ID J:131886]
Haribhai D; Engle D; Meyer M; Donermeyer D; White JM; Williams CB. 2003. A threshold for central T cell tolerance to an inducible serum protein. J Immunol 170(6):3007-14. [PubMed: 12626554] [MGI Ref ID J:128816]
Holst J; Wang H; Eder KD; Workman CJ; Boyd KL; Baquet Z; Singh H; Forbes K; Chruscinski A; Smeyne R; van Oers NS; Utz PJ; Vignali DA. 2008. Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity. Nat Immunol 9(6):658-66. [PubMed: 18469818] [MGI Ref ID J:136207]
Lambe T; Leung JC; Bouriez-Jones T; Silver K; Makinen K; Crockford TL; Ferry H; Forrester JV; Cornall RJ. 2006. CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. J Immunol 177(5):3055-62. [PubMed: 16920942] [MGI Ref ID J:139546]
Lau AW; Biester S; Cornall RJ; Forrester JV. 2008. Lipopolysaccharide-Activated IL-10-Secreting Dendritic Cells Suppress Experimental Autoimmune Uveoretinitis by MHCII-Dependent Activation of CD62L-Expressing Regulatory T Cells. J Immunol 180(6):3889-99. [PubMed: 18322197] [MGI Ref ID J:133030]
Liston A; Gray DH; Lesage S; Fletcher AL; Wilson J; Webster KE; Scott HS; Boyd RL; Peltonen L; Goodnow CC. 2004. Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity. J Exp Med 200(8):1015-26. [PubMed: 15492124] [MGI Ref ID J:93912]
Liston A; Lesage S; Wilson J; Peltonen L; Goodnow CC. 2003. Aire regulates negative selection of organ-specific T cells. Nat Immunol 4(4):350-4. [PubMed: 12612579] [MGI Ref ID J:128567]
Pradhan S; Genebriera J; Denning WL; Felix K; Elmets CA; Timares L. 2006. CD4 T cell-induced, bid-dependent apoptosis of cutaneous dendritic cells regulates T cell expansion and immune responses. J Immunol 177(9):5956-67. [PubMed: 17056520] [MGI Ref ID J:140532]
Rodriguez-Pinto D; Moreno J. 2005. B cells can prime naive CD4+ T cells in vivo in the absence of other professional antigen-presenting cells in a CD154-CD40-dependent manner. Eur J Immunol 35(4):1097-105. [PubMed: 15756646] [MGI Ref ID J:97821]
Shi G; Cox CA; Vistica BP; Tan C; Wawrousek EF; Gery I. 2008. Phenotype switching by inflammation-inducing polarized Th17 cells, but not by Th1 cells. J Immunol 181(10):7205-13. [PubMed: 18981142] [MGI Ref ID J:140933]
Siggs OM; Miosge LA; Yates AL; Kucharska EM; Sheahan D; Brdicka T; Weiss A; Liston A; Goodnow CC. 2007. Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions. Immunity 27(6):912-26. [PubMed: 18093540] [MGI Ref ID J:129169]
Sinha P; Clements VK; Ostrand-Rosenberg S. 2005. Interleukin-13-regulated M2 macrophages in combination with myeloid suppressor cells block immune surveillance against metastasis. Cancer Res 65(24):11743-51. [PubMed: 16357187] [MGI Ref ID J:104344]
Sporri R; Reis e Sousa C. 2005. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol 6(2):163-70. [PubMed: 15654341] [MGI Ref ID J:95652]
Van Parijs L; Biuckians A; Abbas AK. 1998. Functional roles of Fas and Bcl-2-regulated apoptosis of T lymphocytes. J Immunol 160(5):2065-71. [PubMed: 9498742] [MGI Ref ID J:112062]
Van Parijs L; Peterson DA; Abbas AK. 1998. The Fas/Fas ligand pathway and Bcl-2 regulate T cell responses to model self and foreign antigens. Immunity 8(2):265-74. [PubMed: 9492007] [MGI Ref ID J:110425]
Walker LS; Ausubel LJ; Chodos A; Bekarian N; Abbas AK. 2002. CTLA-4 differentially regulates T cell responses to endogenous tissue protein versus exogenous immunogen. J Immunol 169(11):6202-9. [PubMed: 12444125] [MGI Ref ID J:119321]
Zwickey HL; Unternaehrer JJ; Mellman I. 2006. Presentation of self-antigens on MHC class II molecules during dendritic cell maturation. Int Immunol 18(1):199-209. [PubMed: 16361313] [MGI Ref ID J:104201]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
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 |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
|
|
|
Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 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
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.Ordering and Purchasing Information
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice & Services Conditions of Use
“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.
No Liability
In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.
MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.
Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.