Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain NOD/MrkTac Donor Strain FVB/N H2 Haplotype g7 Donating Investigator Dr. Jeffrey A. 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, Ighm (formerly Igh-6), 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.In 2008, a spontaneous mutation to dystonia (Dst) was observed in this colony and may be segregating in cryopreserved stock.
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
003610 B6.129S4-Cd80tm1Shr Cd86tm2Shr/J 003611 B6.129S4-Cd80tm1Shr/J 004673 NOD.129(B6)-Rag1tm1Mom Cd80tm1Shr/JbsJ View Strains carrying other alleles of Cd80 (3 strains)
Strains carrying other alleles of Ighm
002249 B10.129S2(B6)-Ighmtm1Cgn/J 002288 B6.129S2-Ighmtm1Cgn/J 003751 B6;129S4-Ighmtm1Che/J 004349 C.129S2-Ighmtm1Cgn/J 002030 C57BL/6-Tg(Igh-3/Igh-6VD93)1241Ust/J 002029 C57BL/6-Tg(Igl-2MOPC315)1275Ust/J 005020 NOD-Tg(Igh-6/Igh-V281)3Jwt/JwtJ 004639 NOD.129S2(B6)-Ighmtm1Cgn/DoiJ 003903 NOD.129S2-Ighmtm1Cgn/Dvs 006608 NOD.Cg-Ighmtm1Cgn Tg(IghelMD4)4Ccg/DvsJ 005019 NOD.Cg-Tg(Igh-6/Igh-V125)2Jwt/JwtJ 005309 NODCaj.Cg-Ighmtm1Cgn Tg(Igh-VB1-8/Igh-6)2Mjsk/FswJ 005306 NODCaj.Cg-Ighmtm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ View Strains carrying other alleles of Ighm (13 strains)
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View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Tg(Igh-6-Cd80)1Gjf/0
NOD.FVB-Tg(Igh-6-Cd80)1Gjf/JbsJ
- immune system phenotype
- abnormal B cell activation
- splenic transgenic B cells proliferate in cell transfer experiments (MGI Ref ID J:131077)
- abnormal CD8-positive T cell physiology
- CD8+ T cell depletion leads to restoration of B cell numbers (MGI Ref ID J:131077)
- abnormal level of surface class II molecules
- class II expression is increased by 2 fold in splenic B cells (MGI Ref ID J:131077)
- decreased B cell number
- reduction in percentage of circulating B cells beginning at 2 weeks of age (MGI Ref ID J:131077)
- treatment with anti-Cd8 mAb beginning at 3 weeks of age results in an increase in the percentage of B cells to almost control levels (MGI Ref ID J:131077)
- B cells represent 2-3% of cells in blood in contrast to 20-30% found in NOD controls (MGI Ref ID J:131077)
- 2 - 2.5 fold reduction of splenic B cells as compared to NOD controls (MGI Ref ID J:131077)
- immature/mature (B220+, IgM+) B cells reduced more than 10 fold in bone marrow (MGI Ref ID J:131077)
- decreased immature B cell number
- immature/mature (B220+, IgM+) B cells are reduced more than 10 fold in bone marrow (MGI Ref ID J:131077)
- decreased mature B cell number (MGI Ref ID J:131077)
- decreased B-2 B cell number
- percentage of B-2 B cells is decreased greater than 5 fold in the peritoneal cavity, however, numbers of B-1 B cells are not significantly changed (MGI Ref ID J:131077)
- decreased follicular B cell number
- severe depletion of mature (CD2 1ow IgM low) follicular B cells in spleen, however, marginal zone B cells are mostly unaffected (MGI Ref ID J:131077)
- decreased immunoglobulin level
- decreased susceptibility to autoimmune diabetes
- transgenic mice do not develop diabetes (MGI Ref ID J:131077)
- insulitis
- mononuclear infiltration is present, but reduced, in pancreatic islets as compared to control (MGI Ref ID J:131077)
- hematopoietic system phenotype
- abnormal B cell activation
- splenic transgenic B cells proliferate in cell transfer experiments (MGI Ref ID J:131077)
- abnormal bone marrow cell number
- decreased B cell number
- reduction in percentage of circulating B cells beginning at 2 weeks of age (MGI Ref ID J:131077)
- treatment with anti-Cd8 mAb beginning at 3 weeks of age results in an increase in the percentage of B cells to almost control levels (MGI Ref ID J:131077)
- B cells represent 2-3% of cells in blood in contrast to 20-30% found in NOD controls (MGI Ref ID J:131077)
- 2 - 2.5 fold reduction of splenic B cells as compared to NOD controls (MGI Ref ID J:131077)
- immature/mature (B220+, IgM+) B cells reduced more than 10 fold in bone marrow (MGI Ref ID J:131077)
- decreased immature B cell number
- immature/mature (B220+, IgM+) B cells are reduced more than 10 fold in bone marrow (MGI Ref ID J:131077)
- decreased mature B cell number (MGI Ref ID J:131077)
- decreased B-2 B cell number
- percentage of B-2 B cells is decreased greater than 5 fold in the peritoneal cavity, however, numbers of B-1 B cells are not significantly changed (MGI Ref ID J:131077)
- decreased follicular B cell number
- severe depletion of mature (CD2 1ow IgM low) follicular B cells in spleen, however, marginal zone B cells are mostly unaffected (MGI Ref ID J:131077)
- endocrine/exocrine gland phenotype
- insulitis
- mononuclear infiltration is present, but reduced, in pancreatic islets as compared to control (MGI Ref ID J:131077)
- cellular phenotype
- abnormal B cell activation
- splenic transgenic B cells proliferate in cell transfer experiments (MGI Ref ID J:131077)
- decreased immature B cell number
- immature/mature (B220+, IgM+) B cells are reduced more than 10 fold in bone marrow (MGI Ref ID J:131077)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
resistant
Type 1 Diabetes (IDDM) Analysis Strains
NOD Transgenics
Immunology, Inflammation and Autoimmunity Research
Autoimmunity
B cell deficiency
Research Tools
Immunology and Inflammation Research
B cell deficiency
| Allele Symbol | Tg(Igh-6-Cd80)1Gjf | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Gordon J Freeman | ||
| Allele Type | Transgenic (random, expressed) | ||
| 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 | ||
| Expressed Gene | Cd80, CD80 antigen, mouse, laboratory | ||
| Promoter | Ighm, immunoglobulin heavy constant mu, 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] | ||
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 relatedSethna 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
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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