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Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Linda Sherman, The Scripps Research Institute Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcDescription
Transgenic mice are viable, fertile, normal in size and do not display any behavioral abnormalities. FACs analysis indicates expression of HLA-A201 on peripheral blood lymphocytes. The level of expression of this chimeric MHC I molecule in transgenic mice is similar to the observed expression in human PBL's. Diabetes incidence of mice carrying this transgene (88%) is similar to NOD (79%) at 25 weeks of age. Splenocytes from transgenic mice immunized with GAD65 peptides together with MHC class II helper peptide were re-stimulated with peptide pulsed irradiated syngeneic APC?s in-vitro 10 days post immunization Transgenic mice immunized with three different GAD65 peptides (position: 144-149, sequence: LLQEYNWEL; position: 114-122, sequence: VMNILLQYV; and position 573-581, sequence: FLIEEIERL) gave vigorous CTL responses when tested by standard chromium release assays. FACs analysis indicates presence of CFSE expression on CD8+ T-cells in transgenic mice given CFSE-labeled CD8+ T cells in the pancrease, but not in the peripheral or pancreatic lymph nodes 4 days post injection. CFSE-positive CD8+ T-cells were absent in the pancreas, peripheral and pancreatic lymph nodes of wildtype mice. This model provides a tool to identify MHC class I epitopes recognized by CD8+ T cells in type 1 diabetes patients, in addition to testing new therapies focusing on restoring immune tolerance.Development
NOD mice carrying a CD8+ T-cell transgene (HLA-A2/H2-K)1Scr express the alpha 1 and alpha2 domain of the human class 1 molecule, HLA-A201, fused to the alpha 3, transmembrane and cytoplasmic domains of the mouse H-2kb molecule. This transgene was injected into C57BL/6J oocytes. Resulting progeny were backcrossed to NOD for 14 generations. In 2006, The Jackson Laboratory received NOD.Cg-Tg(HLA-A2/H2-K)1Scr/ShrmJ at generation N14.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of H2-K
000368 B6.C-H2bm1/By 006559 B6.C-H2bm1/ByBir-Gusbmps/BrkJ 000256 B6.C-H2bm1/ByBir-Gusbmps/J 001060 B6.C-H2bm1/ByJ 006558 B6.Cg-H2bm1 Tg(GUSB)4Sly/SndsJ 006877 B6.Cg-Ldlrtm1Her Tg(H2-K-AKR1B1)1Tj/J 002432 B6J x B6.C-H2bm1/ByJ-Cdh23v-J/J 002598 C57BL/6-Tg(KLK4mHEL)6Ccg/J 004258 NOD.B6-Tg(KLK4mHEL)6Ccg/Dvs View Strains carrying other alleles of H2-K (9 strains)
Strains carrying other alleles of HLA-A
View Strains carrying other alleles of HLA-A (9 strains)
Congenic Nomenclature
Genetic Quality Control Annual Report
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
HLA-A relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Vaccine Development
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Vaccine Development
| Allele Symbol | Tg(HLA-A2/H2-K)1Scr | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, The Scripps Research Institute | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | CyHLA A2.1/Kb; | ||
| Mutation Made By | Linda Sherman, The Scripps Research Institute | ||
| Strain of Origin | C57BL/6J | ||
| Expressed Gene | H2-K, histocompatibility 2, K region, mouse, laboratory | ||
| Promoter | HLA-A, major histocompatibility complex, class I, A, human | ||
| Molecular Note | The transgene expresses a human-mouse chimeric major histocompatibility class I protein composed of the leader sequence and the alpha1 and alpha2 domains of HLA-A2.1 joined to the alpha3, cytoplasmic and transmembrane domains of H2-Kb. Mice expressing this transgene exhibit HLA-A2.1-restricted CD8 T-cell responses to appropriate antigens. [MGI Ref ID J:91744] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
Vitiello A; Marchesini D; Furze J; Sherman LA; Chesnut RW. 1991. Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex. J Exp Med 173(4):1007-15. [PubMed: 1706750] [MGI Ref ID J:108157]
Tg(HLA-A2/H2-K)1Scr relatedDominguez AL; Lustgarten J. 2008. Implications of aging and self-tolerance on the generation of immune and antitumor immune responses. Cancer Res 68(13):5423-31. [PubMed: 18593945] [MGI Ref ID J:138875]
Irwin MJ; Heath WR; Sherman LA. 1989. Species-restricted interactions between CD8 and the alpha 3 domain of class I influence the magnitude of the xenogeneic response. J Exp Med 170(4):1091-101. [PubMed: 2477484] [MGI Ref ID J:91744]
Sherman LA. 2004. C57BL/6J mice with MHC class I-H2 chimeric transgene can be used to identify HLA-A2.1 restricted peptide epitopes MGI Direct Data Submission :. [MGI Ref ID J:91745]
Smith C; Martinez M; Cooper L; Rist M; Zhong J; Khanna R. 2008. Generating functional CD8(+) T cell memory response under transient CD4(+) T cell deficiency: Implications for vaccination of immunocompromised individuals. Eur J Immunol 38(7):1857-66. [PubMed: 18506880] [MGI Ref ID J:137312]
Zhang Y; Li S; Shan M; Pan X; Zhuang K; He L; Gould K; Tien P. 2007. Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8+ T-cell responses in HLA-A2.1/Kb transgenic mice. Immunology 121(1):105-12. [PubMed: 17244158] [MGI Ref ID J:122636]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| 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 | ||
|---|---|---|
| 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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