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Type Congenic; Mutant Strain; Transgenic; Species laboratory mouse Background Strain NOD/ShiLtJ H2 Haplotype g7 Donating Investigator Linda Sherman, The Scripps Research Institute Appearance
pink-eyed, albino
Related Genotype: A/A Tyrc/TyrcDescription
Transgenic mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The diabetes rate in transgenic females is similar to NOD females. FACS analysis using anti-HA antibodies indicates similar levels of HA expression on pancreatic beta cells as BALB-InsHA (Stock No. 005533). Tetramer (KdHA) binding and dose titration analysis indicate CD8+ T cells obtained from transgenic mice exhibit high avidity for HA. Irradiated transgenic females adoptively transferred with transgenic CTL's exhibit rapid diabetes onset, whereas irradiated, non-transgenic NOD females do not become diabetic indicating HA antigen specificity. This model is useful for studying CD8+ T cell peripheral tolerance deficiency (Kreuwel et al, 2001).Development
NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ expresses influenza hemagglutinin (HA) molecule from the well characterized influenza A/PR/8/34 under the control of the rat insulin 2 promoter (Ins2). This transgene was injected into (C57BL/6J x SJL)F2 oocytes. Resulting progeny from founder line 2917-5 was backcrossed to H2d strains BALB/cBy for 10 generations and B10.D2 for 10 generations or to NOD/Shi, H2g7, for 13 generations (Kreuwel et al., 2001). In 2005, the Jackson Laboratory received NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ at generation N20.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Strains carrying Tg(Ins2-HA)165Bri allele
005534 B10.Cg-H2d Tg(Ins2-HA)165Bri/ShrmJ 005533 C.Cg-Tg(Ins2-HA)165Bri/ShrmJ View Strains carrying Tg(Ins2-HA)165Bri (2 strains)
Strains carrying other alleles of Ins2
View Strains carrying other alleles of Ins2 (40 strains)
Congenic Nomenclature
Genetic Quality Control Annual Report
Research Applications
This mouse can be used to support research in many areas including:
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Rearranged Antigen-Specific T Cell Receptor Transgenes
T Cell Receptor Signaling Defects
Research Tools
Cancer Research (specific T cell deficiency)
Cancer Research (tumor immunology)
Diabetes and Obesity Research
Immunology and Inflammation Research (T Cell Receptor Transgenics)
| Allele Symbol | Tg(Ins2-HA)165Bri | ||
|---|---|---|---|
| Allele Name | transgene insertion 165, Ralph Brinster | ||
| Common Name(s) | 2917-5; Ins-HA; InsHA; Tg(Ins-2,HA)Bri165; | ||
| Mutation Made By | Ralph Brinster, University of Pennsylvania | ||
| Expressed Gene | HA, influenza hemagglutinin, | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | The transgenic construct consisted of the rat insulin 2 promoter fused to sequence encoding influenza hemagglutinin (HA) followed by the 3' untranslated region and polyadenylation signal from the H2-Ea. HA was from influenza A/PR/8/34. This rat insulin 2 promoter is active in pancreatic beta-cells. [MGI Ref ID J:86430] | ||
Genotyping Protocols
Tg(Ins2-HA)165Bri, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Kreuwel HT; Biggs JA; Pilip IM; Pamer EG; Lo D; Sherman LA. 2001. Defective CD8+ T cell peripheral tolerance in nonobese diabetic mice. J Immunol 167(2):1112-7. [PubMed: 11441123] [MGI Ref ID J:107321]
Tg(Ins2-HA)165Bri related
Apostolou I; Hao Z; Rajewsky K; von Boehmer H. 2003. Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes. J Exp Med 198(7):1103-6. [PubMed: 14530378] [MGI Ref ID J:85985]Bercovici N; Heurtier A; Vizler C; Pardigon N; Cambouris C; Desreumaux P; Liblau R. 2000. Systemic administration of agonist peptide blocks the progression of spontaneous CD8-mediated autoimmune diabetes in transgenic mice without bystander damage. J Immunol 165(1):202-10. [PubMed: 10861053] [MGI Ref ID J:62874]
Hernandez J; Aung S; Redmond WL; Sherman LA. 2001. Phenotypic and functional analysis of CD8(+) T cells undergoing peripheral deletion in response to cross-presentation of self-antigen. J Exp Med 194(6):707-17. [PubMed: 11560988] [MGI Ref ID J:100011]
Kreuwel HT; Morgan DJ; Krahl T; Ko A; Sarvetnick N; Sherman LA. 1999. Comparing the relative role of perforin/granzyme versus Fas/Fas ligand cytotoxic pathways in CD8+ T cell-mediated insulin-dependent diabetes mellitus. J Immunol 163(8):4335-41. [PubMed: 10510373] [MGI Ref ID J:100013]
Lo D; Freedman J; Hesse S; Palmiter RD; Brinster RL; Sherman LA. 1992. Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects both CD4+ and CD8+ T cells. Eur J Immunol 22(4):1013-22. [PubMed: 1348026] [MGI Ref ID J:86430]
Lyman MA; Aung S; Biggs JA; Sherman LA. 2004. A spontaneously arising pancreatic tumor does not promote the differentiation of naive CD8+ T lymphocytes into effector CTL. J Immunol 172(11):6558-67. [PubMed: 15153470] [MGI Ref ID J:90532]
Lyman MA; Nugent CT; Marquardt KL; Biggs JA; Pamer EG; Sherman LA. 2005. The fate of low affinity tumor-specific CD8+ T cells in tumor-bearing mice. J Immunol 174(5):2563-72. [PubMed: 15728462] [MGI Ref ID J:97745]
Martinez X; Kreuwel HT; Redmond WL; Trenney R; Hunter K; Rosen H; Sarvetnick N; Wicker LS; Sherman LA. 2005. CD8+ T Cell Tolerance in Nonobese Diabetic Mice Is Restored by Insulin-Dependent Diabetes Resistance Alleles. J Immunol 175(3):1677-85. [PubMed: 16034108] [MGI Ref ID J:100008]
Morgan DJ; Kreuwel HT; Fleck S; Levitsky HI; Pardoll DM; Sherman LA. 1998. Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity. J Immunol 160(2):643-51. [PubMed: 9551898] [MGI Ref ID J:45169]
Morgan DJ; Kurts C; Kreuwel HT; Holst KL; Heath WR; Sherman LA. 1999. Ontogeny of T cell tolerance to peripherally expressed antigens. Proc Natl Acad Sci U S A 96(7):3854-8. [PubMed: 10097127] [MGI Ref ID J:109899]
Morgan DJ; Liblau R; Scott B; Fleck S; McDevitt HO; Sarvetnick N; Lo D; Sherman LA. 1996. CD8(+) T cell-mediated spontaneous diabetes in neonatal mice. J Immunol 157(3):978-83. [PubMed: 8757600] [MGI Ref ID J:99756]
Morgan DJ; Nugent CT; Raveney BJ; Sherman LA. 2004. In a transgenic model of spontaneous autoimmune diabetes, expression of a protective class II MHC molecule results in thymic deletion of diabetogenic CD8+ T cells. J Immunol 172(2):1000-8. [PubMed: 14707073] [MGI Ref ID J:100010]
Pauza ME; Nguyen A; Wolfe T; Ho IC; Glimcher LH; von Herrath M; Lo D. 2001. Variable effects of transgenic c-Maf on autoimmune diabetes. Diabetes 50(1):39-46. [PubMed: 11147792] [MGI Ref ID J:133138]
Redmond WL; Marincek BC; Sherman LA. 2005. Distinct requirements for deletion versus anergy during CD8 T cell peripheral tolerance in vivo. J Immunol 174(4):2046-53. [PubMed: 15699134] [MGI Ref ID J:100009]
Redmond WL; Wei CH; Kreuwel HT; Sherman LA. 2008. The apoptotic pathway contributing to the deletion of naive CD8 T cells during the induction of peripheral tolerance to a cross-presented self-antigen. J Immunol 180(8):5275-82. [PubMed: 18390708] [MGI Ref ID J:134242]
Smith SS; Patterson T; Pauza ME. 2005. Transgenic Ly-49A inhibits antigen-driven T cell activation and delays diabetes. J Immunol 174(7):3897-905. [PubMed: 15778344] [MGI Ref ID J:97982]
VanOosten RL; Griffith TS. 2007. Activation of tumor-specific CD8+ T Cells after intratumoral Ad5-TRAIL/CpG oligodeoxynucleotide combination therapy. Cancer Res 67(24):11980-90. [PubMed: 18089829] [MGI Ref ID J:129272]
Currently there no information available for this strain. This may be due to the supply level of this strain.
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
| 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 | ||
| 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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