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| These transgenic mice express an interspecies hybrid class I MHC gene, AAD, which contains the alpha-1 and alpha-2 domains of the human HLA-A2.1 gene and the alpha-3 transmembrane and cytoplasmic domains of the mouse H-2Dd gene, under the direction of the human HLA-A2.1 promoter. This transgenic strain enables the modeling of human T cell immune responses to HLA-A2 presented antigens, and identification of those antigens, and is an important preclinical model for design and testing of vaccines for infectious diseases or cancer therapy involving optimal stimulation of Cd8+ cytolytic T cells. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
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Description
Strain Information
Former Names B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/J (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 Hemizygote x Hemizygote (Female x Male) 01-MAR-06 Species laboratory mouse Generation NE11N1F1 (24-MAR-11)
Generation DefinitionsDonating Investigator Dr. Victor H. Engelhard, University of Virginia Description
Mice homozygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These transgenic mice express an interspecies hybrid class I MHC gene, AAD, which contains the alpha-1 and alpha-2 domains of the human HLA-A2.1 gene and the alpha-3 transmembrane and cytoplasmic domains of the mouse H-2Dd gene, under the direction of the human HLA-A2.1 promoter. Immunodetection of the HLA-A2.1 recombinant transgene established that expression was at equivalent levels to endogenous mouse class I molecules. The mouse alpha-3 domain expression enhances the immune response in this system. Compared to unmodified HLA-A2.1, the chimeric HLA-A2.1/H2-Dd MHC Class I molecule mediates efficient positive selection of mouse T cells to provide a more complete T cell repertoire capable of recognizing peptides presented by HLA-A2.1 Class I molecules. The peptide epitopes presented and recognized by mouse T cells in the context of the HLA-A2.1/H2-Dd class I molecule are the same as those presented in HLA-A2.1+ humans. This transgenic strain enables the modeling of human T cell immune responses to HLA-A2 presented antigens, and identification of those antigens. This transgenic strain is an important preclinical model for design and testing of vaccines for infectious diseases or cancer therapy involving optimal stimulation of Cd8+ cytolytic T cells.Development
A transgenic construct containing the leader, alpha-1 and alpha-2 domains of human HLA-A2.1 and the alpha-3 transmembrane and cytoplasmic domains of mouse H-2Dd was injected into fertilized (C57BL/6 X CBA/Ca)F1 mouse eggs. Founder animals were bred with C57BL/6 mice.SNP (single nucleotide polymorphism) analysis performed by The Jackson Laboratory revealed that the Donating Investigator used C57BL/6N (2 of 5 markers segregating) in the development of the strain. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J at least once to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of HLA-A
View Strains carrying other alleles of HLA-A (12 strains)
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Major Histocompatibility Complex, Class I, A; HLA-A (HLA-A)
Severe Cutaneous Adverse Reaction, Susceptibility to (HLA-A)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(HLA-A/H2-D)2Enge/?
(C57BL/6 x CBA)F1
- immune system phenotype
- abnormal cytotoxic T cell physiology
- CD8 T cells from influenza infected transgenic mice lyse target cells presenting influenza peptide on either human HLA-A2.1 (MHC-I) or chimeric human mouse HLA-A/H2-D (MHC-I) complexes (MGI Ref ID J:31937)
- CD8 T cells lyse target cells expressing the chimeric MHC-I complex with 10-fold higher efficiency compared to target cell expressing the human MHC-I complex (MGI Ref ID J:31937)
- abnormal negative T cell selection
- T cells that recognize the human MHC-1 complex HLA-A2.1 are not negatively selected (MGI Ref ID J:31937)
- abnormal positive T cell selection
- positive selection of T cells capable of responding to antigen presented by chimeric MHC-1 complexes is enhanced compared to selection in Tg(HLA-A2.1)1Enge mice that express human MHC-1 (MGI Ref ID J:31937)
- the chimeric MHC Class I molecule mediates efficient positive selection of mouse T cells to provide a more complete T cell repertoire capable of recognizing peptides presented by HLA-A2.1 Class I molecules. (MGI Ref ID J:31937)
- The peptide epitopes presented and recognized by mouse T cells in the context of the HLA-A2.1/H2-Dd class I molecule are the same as those presented in HLA-A2.1+ humans. (MGI Ref ID J:31937)
- hematopoietic system phenotype
- abnormal negative T cell selection
- T cells that recognize the human MHC-1 complex HLA-A2.1 are not negatively selected (MGI Ref ID J:31937)
- abnormal positive T cell selection
- positive selection of T cells capable of responding to antigen presented by chimeric MHC-1 complexes is enhanced compared to selection in Tg(HLA-A2.1)1Enge mice that express human MHC-1 (MGI Ref ID J:31937)
- the chimeric MHC Class I molecule mediates efficient positive selection of mouse T cells to provide a more complete T cell repertoire capable of recognizing peptides presented by HLA-A2.1 Class I molecules. (MGI Ref ID J:31937)
- The peptide epitopes presented and recognized by mouse T cells in the context of the HLA-A2.1/H2-Dd class I molecule are the same as those presented in HLA-A2.1+ humans. (MGI Ref ID J:31937)
- cellular phenotype
- abnormal negative T cell selection
- T cells that recognize the human MHC-1 complex HLA-A2.1 are not negatively selected (MGI Ref ID J:31937)
- abnormal positive T cell selection
- positive selection of T cells capable of responding to antigen presented by chimeric MHC-1 complexes is enhanced compared to selection in Tg(HLA-A2.1)1Enge mice that express human MHC-1 (MGI Ref ID J:31937)
- the chimeric MHC Class I molecule mediates efficient positive selection of mouse T cells to provide a more complete T cell repertoire capable of recognizing peptides presented by HLA-A2.1 Class I molecules. (MGI Ref ID J:31937)
- The peptide epitopes presented and recognized by mouse T cells in the context of the HLA-A2.1/H2-Dd class I molecule are the same as those presented in HLA-A2.1+ humans. (MGI Ref ID J:31937)
This mouse can be used to support research in many areas including:
Immunology, Inflammation and Autoimmunity Research
HLA transgenics
Research Tools
Cancer Research
production of B and T cells, antibodies, and hybridomas
production of T cells and hybridoma
tumor immunology
xenograft/transplant host
Developmental Biology Research
transplantation marker for embryonic and adult tissue
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: cell marker for bone marrow transplantation
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(HLA-A/H2-D)2Enge | ||
|---|---|---|---|
| Allele Name | transgene insertion 2, Victor H Engelhard | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | AAD mice; | ||
| Mutation Made By | Dr. Victor Engelhard, University of Virginia | ||
| Strain of Origin | (C57BL/6 x CBA/Ca)F1 | ||
| Expressed Gene | HLA-A, major histocompatibility complex, class I, A, human | ||
| Promoter | HLA-A2.1, major histocompatibility complex, class I, subtype A2.1, human | ||
| General Note | Phenotypic Similarity to Human Syndrome: Spontaneous Melanoma (J:130879) | ||
| Molecular Note | Transgenic mice express an interspecies hybrid class I MHC gene, AAD, which contains the alpha-1 and alpha-2 domains of the human HLA-A2.1 gene and the alpha-3 transmembrane and cytoplasmic domains of the murine H-2D gene, under the direction of the human HLA-A2.1 promoter. Immunodetection of the HLA-A2.1 recombinant transgene established that expression was at equivalent levels to endogenous murine class I molecules and to similar transgenic strains. [MGI Ref ID J:31937] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(HLA-A/H2-D), QPCR
Tg(HLA-A/H2-D), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Newberg MH; Smith DH; Haertel SB; Vining DR; Lacy E; Engelhard VH. 1996. Importance of MHC class 1 alpha2 and alpha3 domains in the recognition of self and non-self MHC molecules. J Immunol 156(7):2473-80. [PubMed: 8786307] [MGI Ref ID J:31937]
Additional References
Tg(HLA-A/H2-D)2Enge relatedColella TA; Bullock TN; Russell LB; Mullins DW; Overwijk WW; Luckey CJ; Pierce RA; Restifo NP; Engelhard VH. 2000. Self-tolerance to the murine homologue of a tyrosinase-derived melanoma antigen: implications for tumor immunotherapy. J Exp Med 191(7):1221-32. [PubMed: 10748239] [MGI Ref ID J:149581]
Eyles J; Puaux AL; Wang X; Toh B; Prakash C; Hong M; Tan TG; Zheng L; Ong LC; Jin Y; Kato M; Prevost-Blondel A; Chow P; Yang H; Abastado JP. 2010. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J Clin Invest 120(6):2030-9. [PubMed: 20501944] [MGI Ref ID J:161630]
Gregg RK; Nichols L; Chen Y; Lu B; Engelhard VH. 2010. Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase-specific TCR transgenic mice. J Immunol 184(4):1909-17. [PubMed: 20083666] [MGI Ref ID J:159480]
Hong M; Puaux AL; Huang C; Loumagne L; Tow C; Mackay C; Kato M; Prevost-Blondel A; Avril MF; Nardin A; Abastado JP. 2011. Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. Cancer Res 71(22):6997-7009. [PubMed: 21948969] [MGI Ref ID J:178007]
Lengagne R; Graff-Dubois S; Garcette M; Renia L; Kato M; Guillet JG; Engelhard VH; Avril MF; Abastado JP; Prevost-Blondel A. 2008. Distinct role for CD8 T cells toward cutaneous tumors and visceral metastases. J Immunol 180(1):130-7. [PubMed: 18097012] [MGI Ref ID J:130879]
Madsen CB; Petersen C; Lavrsen K; Harndahl M; Buus S; Clausen H; Pedersen AE; Wandall HH. 2012. Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response. PLoS One 7(11):e50139. [PubMed: 23189185] [MGI Ref ID J:195006]
Nichols LA; Chen Y; Colella TA; Bennett CL; Clausen BE; Engelhard VH. 2007. Deletional self-tolerance to a melanocyte/melanoma antigen derived from tyrosinase is mediated by a radio-resistant cell in peripheral and mesenteric lymph nodes. J Immunol 179(2):993-1003. [PubMed: 17617591] [MGI Ref ID J:149399]
Qian J; Dong Y; Pang YY; Ibrahim R; Berzofsky JA; Schiller JT; Khleif SN. 2006. Combined prophylactic and therapeutic cancer vaccine: enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA-A2 mice. Int J Cancer 118(12):3022-9. [PubMed: 16425257] [MGI Ref ID J:112324]
Tewalt EF; Cohen JN; Rouhani SJ; Guidi CJ; Qiao H; Fahl SP; Conaway MR; Bender TP; Tung KS; Vella AT; Adler AJ; Chen L; Engelhard VH. 2012. Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood 120(24):4772-82. [PubMed: 22993390] [MGI Ref ID J:192127]
Toh B; Wang X; Keeble J; Sim WJ; Khoo K; Wong WC; Kato M; Prevost-Blondel A; Thiery JP; Abastado JP. 2011. Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol 9(9):e1001162. [PubMed: 21980263] [MGI Ref ID J:184038]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry Founder mice were backcrossed to C57BL/6 animals for at least 10 generation before being made homozygous. Mating System Hemizygote x Hemizygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(HLA-A/H2-D)2Enge $232.00 Female or Male Homozygous for Tg(HLA-A/H2-D)2Enge
Price per Pair (US dollars $) Pair Genotype $464.00 Hemizygous for Tg(HLA-A/H2-D)2Enge x Hemizygous for Tg(HLA-A/H2-D)2Enge Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(HLA-A/H2-D)2Enge $301.60 Female or Male Homozygous for Tg(HLA-A/H2-D)2Enge
Price per Pair (US dollars $) Pair Genotype $603.20 Hemizygous for Tg(HLA-A/H2-D)2Enge x Hemizygous for Tg(HLA-A/H2-D)2Enge Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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|
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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 Information
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