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| This congenic NOD strain contains a transgene encoding murine Cd80 controlled by IgM enhancer and promoter elements and is commonly referred to as NOD.B7-1B Tg. The donating investigator reports that this diabetes resistant strain expresses high levels of the transgene on B cells, but not on T-cells. Circulating, speenic, and bone marrow B cells are significantly reduced. This strain may be used to study autoreactive T cell activation, B cell deletion and the role of B7 co stimulatory molecules in autoimmunity, specifically Type 1 Diabetes. | |||||||||||
Type Congenic; Mutant Strain; Transgenic; Mating System Noncarrier x Hemizygote (Female x Male) Species laboratory mouse Background Strain NOD/MrkTac Donor Strain FVB/N H2 Haplotype g7 Generation N15+N1 (04-MAR-08) Donating Investigator Jeffrey Bluestone, University of California, San Francisco Appearance
albino
Related Genotype: A/A Tyrc/TyrcDescription
Transgenic mice are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities. High levels of the transgene are expressed on B cells, but not on T cells. At 30 weeks of age transgenic mice are diabetes resistant and insulitis was significantly reduced when compared with wildtype NOD controls. When compared to wildtype NOD controls, the circulating B cells in congenic NOD transgenic mice is 2-3 fold lower in 2 week old mice and 10 fold lower in 5-6 week old mice and persists throughout life. Significantly reduced percentage of B cells were found in the spleen and bone marrow. Analysis of bone marrow shows the more mature B cell subsets (B220+, IgM+) are affected. Elisa tests indicate reduced circulating levels of all Ig types, Igh-6 (IgM), Igh-3 (IgG2b), and Ighg1 (IgG1) in the serum of transgenic mice. MHC class II expression of splenic B cells was significantly increased by more than 2 fold, indicating features of an activated B cell phenotype, in NOD-H2g7 transgenic mice when compared to NOD wildtype and NOD.-H2b transgenic mice.This strain may be used to study autoreactive T cell activation and B cell deletion and the role of B7 costimulatory molecules in autoimmunity, specifically Type 1 Diabetes.
Development
The Igh-6-CD80 transgenic construct, commonly called B7-1B Tg, encodes a murine Cd80 cDNA, containing the complete coding region that lacks the 2' and 5' UTR's, controlled by IgM enhancer and promoter elements. To enhance expression of the transgene, the construct additionally contains a mutated non-expressible segment of the human growth hormone gene. The transgenic construct was microinjected into FVB/N embryos. FVB/N transgenic mice from line B-B7-1 were backcrossed to NOD/MrkTac mice for more than 15 generations. In 2007, the T1DR received transgenic mice at generation N15+ and backcrossed to NOD/ShiLtJ (Stock No. 001976) once prior to sibling mating.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Cd80
View Strains carrying other alleles of Cd80 (5 strains)
Strains carrying other alleles of Igh-6
View Strains carrying other alleles of Igh-6 (12 strains)
Congenic Nomenclature
Research Applications
This mouse can be used to support research in many areas including:
Igh-6 relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) (resistant)
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)
Immunology and Inflammation Research
Autoimmunity (B cell deficiency)
Research Tools
Immunology and Inflammation Research (B cell deficiency)
Immunology and Inflammation Research
Immunodeficiency (B cell deficiency)
Research Tools
Cancer Research (B cell deficiency)
Immunology and Inflammation Research (B cell deficiency)
| Allele Symbol | Tg(Igh-6-Cd80)1Gjf | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Gordon J Freeman | ||
| Common Name(s) | B.B7-1; B7-1 transgene; B7-1T Tg; T.B7-1; | ||
| Mutation Made By | Gordon Freeman, Harvard Medical School | ||
| Strain of Origin | FVB | ||
| ES Cell Line Strain | 129 | ||
| Expressed Gene | Cd80, CD80 antigen, mouse, laboratory | ||
| Promoter | Igh-6, immunoglobulin heavy chain 6 (heavy chain of IgM), mouse, laboratory | ||
| Molecular Note | The transgene was constructed with the Cd80 cDNA containing the complete coding region (but lacking the 2' and 5' UTRs) under control of the Igh-6 enhancer and promoter elements. The construct also contained a mutated nonexpressible segment of the human growth hormone gene included to enhance transgene expression. [MGI Ref ID J:112474] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
Bour-Jordan H; Salomon BL; Thompson HL; Santos R; Abbas AK; Bluestone JA. 2007. Constitutive expression of B7-1 on B cells uncovers autoimmunity toward the B cell compartment in the nonobese diabetic mouse. J Immunol 179(2):1004-12. [PubMed: 17617592] [MGI Ref ID J:131077]
Tg(Igh-6-Cd80)1Gjf related
Sethna MP; van Parijs L; Sharpe AH; Abbas AK; Freeman GJ. 1994. A negative regulatory function of B7 revealed in B7-1 transgenic mice. Immunity 1(5):415-21. [PubMed: 7533646] [MGI Ref ID J:112474]Van Parijs L; Sethna MP; Schweitzer AN; Borriello F; Sharpe AH; Abbas AK. 1997. Functional consequences of dysregulated B7-1 (CD80) and B7-2 (CD86) expression in B or T lymphocytes of transgenic mice. J Immunol 159(11):5336-44. [PubMed: 9548473] [MGI Ref ID J:44271]
Yu X; Fournier S; Allison JP; Sharpe AH; Hodes RJ. 2000. The role of B7 costimulation in CD4/CD8 T cell homeostasis. J Immunol 164(7):3543-53. [PubMed: 10725709] [MGI Ref ID J:112266]
Animal Health Reports
Room Number FGB29
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $54.00 Female or Male Hemizygous for Tg(Igh-6-Cd80)1Gjf *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $108.00 Hemizygous for Tg(Igh-6-Cd80)1Gjf x Noncarrier $108.00 Noncarrier x Hemizygous for Tg(Igh-6-Cd80)1Gjf
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $70.20 Female or Male Hemizygous for Tg(Igh-6-Cd80)1Gjf *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $140.40 Hemizygous for Tg(Igh-6-Cd80)1Gjf x Noncarrier $140.40 Noncarrier x Hemizygous for Tg(Igh-6-Cd80)1Gjf
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
| 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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