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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
Description
Strain Information
Former Names C.B6-Tg(Ins2-NP)25-3Olds/MvhJ (Changed: 01-APR-05 ) C.Cg-Tg(Ins2-NP)25-3Scr/MvhJ (Changed: 31-MAR-05 ) Type Congenic; Mutant Strain; Transgenic; Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Background Strain BALB Donor Strain (C57BL/6 x BALB)F2 H2 Haplotype d Donating Investigator Matthais von Herrath, La Jolla Institute for Allergy and Immun Appearance
albino
Related Genotype: A/A Tyrc/ TyrcDescription
Transgenic mice were created with the Lymphocytic choriomeningitis virus (LCMV) nucleoprotein(NP) or glycoprotein(GP) under the control of the rat insulin promoter. Northern blot analysis identifies a 3kb band expected of the transgene and SV40 processing signals in the pancreas (Oldstone et al., 1991). Ins2-NP expression was determined in the pancreas and thymus by RT-PCR (von Herrath et al 1994). Tg(Ins2-NP)25-3Olds untreated mice rarely develop insulin-dependent diabetes mellitus (IDDM). When challenged with LCMV they develop IDDM. The B6.Cg -Tg(Ins2-NP)25-3Olds mice (H2b) exhibit a slower (30-120 days) onset of IDDM than the C.Cg-Tg(Ins2-NP)25-3Olds mice (H2d) (10-21 days) or the B6.Cg-Tg(Ins2-GP) 34-20Olds mice (H2b) (10-14 days) (Oldstone et al.,1991, Homann et al.,1999). Thymic expression of nucleoprotein has been shown to be responsible for this delayed onset of IDDM. Thymi from newborn B6.Cg-Tg(Ins2-NP)25-3Olds transplanted into hosts homozygous for Prkdcscid fail to produce a primary CTL response when challenged with LCMV, although thymi transplanted from C.Cg-Tg(Ins2-NP)25-3Olds mice mount a response. CD8 T cells are required for IDDM development in both nucleoprotein and glycoprotein transgenic mice, as is interferon gamma. In interferon gamma deficient transgenicsstimulated with LCMV, CTLs were present in the pancreas and around the islets of Langerhans, but did not infiltrate the islets. Additionally, nucleoprotein transgenic animals require the presence of CD4 T cells. (von Herrath, et al, 1994 and 1997)Diabetes can be prevented in the C.Cg-Tg(Ins2-NP)25-3Olds (H2dmice after its induction by LCMV infection through oral insulin treatment and this model has proven that bystander suppression of autoaggressive CD8 T cells can occur in the pancreatic draining lymph node (Homann et al., 1999).
A single dose injection of anti CD80, anti CD86 or anti CD80/anti CD86 antibodies does not prevent LCMV induced diabetes in either the NP or GP transgenic mice. LCMV challenged GP transgenic mice are partially protected from diabetes by anti CD80 antibodies and completely protected by anti CD86 or anti CD80/CD86 antibodies injected daily for 14 days. However, LCMV challenged NP transgenic mice have accelerated diabetes onset when treated with anti CD80/CD86 antibodies injected daily for 14 days. LCMV induced diabetes is prevented in NP and GP transgenic mice treated with anti TNFRSF5 when treated within a defined time window. Splenocytes from these protected mice adoptively transferred disease resistance to LCMV- challenged pre diabetic GP transgenic mice. The cells thatconfer protection express ITGAX5, NK1.1 and DX5. The spleens of anti TNFRSF5 protected mice have an increased population of ITGAX5 expressing cells. When this population of cells is further fractionated into ITGAX5+, DX5+ cells, the recipient mice acquire protection from diabetes. (Homann et al., 2002)
Development
C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ expresses the lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) under control of the rat insulin promoter, (Ins2, commonly designated RIP). The transgene was first inserted by Oldstone, et al (1991) into C57BL/6 (H2b) x Balb/WEHI (H2d) F2 oocytes. Line 25-3, maintained by Herrath et al., (1994, 2000) has been backcrossed to BALB/c (H2d) for at least 10 generations. This strain arrived at The Jackson Laboratory in 2003 and is maintained as hemizygous.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000651 BALB/cJ | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(Ins2-NP)25-3Olds allele
004826 B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ View Strains carrying Tg(Ins2-NP)25-3Olds (1 strain)
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
Related Disease (OMIM) Terms
Diabetes Mellitus, Insulin-Dependent; IDDM Mammalian Phenotype Terms assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Ins2-NP)25-3Olds/0
involves: BALB/c * C57BL/6
- homeostasis/metabolism phenotype
- decreased circulating insulin level (MGI Ref ID J:81287)
- hypoinsulinemia is exhibited by transgenic mice accompanying increased glucose levels and islet infiltration
- increased circulating glucose level (MGI Ref ID J:81284)
- 3% of transgenic mice develop diabetes when followed for 10-12 months
- 93% of transgenic mice develop diabetes (hyperglycemia of >250 mg/dl glucose and islets infiltrated with mononuclear cells) after being infected with LCMV
- mice are considered diabetic after a blood glucose measure of >300 mg/dl
- endocrine/exocrine gland phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:81287)
- pancreata of diabetic transgenic mice show swollen islets with a ground glass appearance
- mononuclear cells begin infiltrating the islets 10 days after viral challenge and are apparent in most transgenic mice after 30 days
- after viral challenge, mononuclear cells infiltrate the islets of transgenic mice bred onto a BALB/c background at 14-21days, while mice bred onto a C57BL/6 background show infiltrates at 21-60 days
- digestive/alimentary phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:81287)
- pancreata of diabetic transgenic mice show swollen islets with a ground glass appearance
- mononuclear cells begin infiltrating the islets 10 days after viral challenge and are apparent in most transgenic mice after 30 days
- after viral challenge, mononuclear cells infiltrate the islets of transgenic mice bred onto a BALB/c background at 14-21days, while mice bred onto a C57BL/6 background show infiltrates at 21-60 days
- immune system phenotype
- decreased susceptibility to autoimmune diabetes (MGI Ref ID J:81287)
- depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes
- increased susceptibility to autoimmune diabetes (MGI Ref ID J:81287)
- 3% of transgenic mice develop diabetes when followed for 10-12 months
- 93% of transgenic mice develop diabetes (evidenced by hyperglycemia with glucose levels of >300 mg/dl and islets infiltrated with mononuclear cells) after being infected with LCMV
- after viral (LCMV) challenge, transgenic mice bred onto a C57BL/6 background develop diabetes in 3-5 months, whereas transgenic mice bred onto a BALB/c background develop diabetes sooner, at 1-2 months
Research Applications
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Research Tools
Diabetes and Obesity Research
Immunology and Inflammation Research (T Cell Receptor Transgenics)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Ins2-NP)25-3Olds | ||
|---|---|---|---|
| Allele Name | transgene insertion 25-3, Michael BA Oldstone, MD | ||
| Common Name(s) | RIP NP 25-3; RIP-LCMV; RIP-LCMV NP; | ||
| Mutation Made By | Michael Oldstone, The Scripps Research Institute | ||
| Strain of Origin | C57BL/6 x BALB/c | ||
| Expressed Gene | NP, lymphocytic choriomeningitis virus nucleoprotein, viral | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | This transgene encodes the nucleoprotein (NP) from Armstrong's clone of the lymphocytic choriomeningitis virus (LCMV) regulated by the rat insulin promoter. Upstream of the NP cDNA are 660 base pairs of regulatory elements in addition to the rat insulin promoter. Downstream of the NP c-DNA is the SV40 small T-antigen intron and late polyadenylation signal. A stable transcript of the expected size was present in the pancreas, as determined by Northern blot analysis. RT-PCR analysis demonstrated that the transcript was expressed in pancreas and thymus, but not the spleen, brain, liver, kidney, heart, muscle or lung. In a T cell recognition assay, LCMV-specific cytotoxic T lymphocytes were shown to migrate specifically to the islets of Langerhans of transgenic mice, but not in control mice. [MGI Ref ID J:81284] [MGI Ref ID J:81287] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Ins2-NP)25-3Olds, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Oldstone MB; Nerenberg M; Southern P; Price J; Lewicki H. 1991. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65(2):319-31. [PubMed: 1901765] [MGI Ref ID J:81284]
Additional References
von Herrath MG; Dockter J; Oldstone MB. 1994. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1(3):231-42. [PubMed: 7889411] [MGI Ref ID J:81287]
Tg(Ins2-NP)25-3Olds related
Bresson D; Togher L; Rodrigo E; Chen Y; Bluestone JA; Herold KC; von Herrath M. 2006. Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J Clin Invest 116(5):1371-81. [PubMed: 16628253] [MGI Ref ID J:108962]Holz A; Bot A; Coon B; Wolfe T; Grusby MJ; von Herrath MG. 1999. Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence. J Immunol 163(10):5374-82. [PubMed: 10553062] [MGI Ref ID J:107047]
Holz A; Brett K; Oldstone MB. 2001. Constitutive beta cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes. J Clin Invest 108(12):1749-58. [PubMed: 11748258] [MGI Ref ID J:134571]
Holz A; Dyrberg T; Hagopian W; Homann D; von Herrath M; Oldstone MB. 2000. Neither B lymphocytes nor antibodies directed against self antigens of the islets of Langerhans are required for development of virus-induced autoimmune diabetes. J Immunol 165(10):5945-53. [PubMed: 11067957] [MGI Ref ID J:118383]
Homann D; Holz A; Bot A; Coon B; Wolfe T; Petersen J; Dyrberg TP; Grusby MJ; von Herrath MG. 1999. Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway. Immunity 11(4):463-72. [PubMed: 10549628] [MGI Ref ID J:96857]
Homann D; Jahreis A; Wolfe T; Hughes A; Coon B; van Stipdonk MJ; Prilliman KR; Schoenberger SP; von Herrath MG. 2002. CD40L blockade prevents autoimmune diabetes by induction of bitypic NK/DC regulatory cells. Immunity 16(3):403-15. [PubMed: 11911825] [MGI Ref ID J:96858]
Hugues S; Mougneau E; Ferlin W; Jeske D; Hofman P; Homann D; Beaudoin L; Schrike C; Von Herrath M; Lehuen A; Glaichenhaus N. 2002. Tolerance to islet antigens and prevention from diabetes induced by limited apoptosis of pancreatic beta cells. Immunity 16(2):169-81. [PubMed: 11869679] [MGI Ref ID J:132052]
Martinic MM; Juedes AE; Bresson D; Homann D; Skak K; Huber C; Ling E; Ejrnaes M; Wolfe T; Togher L; Christen U; von Herrath MG. 2007. Minimal impact of a de novo-expressed beta-cell autoantigen on spontaneous diabetes development in NOD mice. Diabetes 56(4):1059-68. [PubMed: 17395746] [MGI Ref ID J:122080]
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]
Rhode A; Pauza ME; Barral AM; Rodrigo E; Oldstone MB; von Herrath MG; Christen U. 2005. Islet-specific expression of CXCL10 causes spontaneous islet infiltration and accelerates diabetes development. J Immunol 175(6):3516-24. [PubMed: 16148094] [MGI Ref ID J:116715]
Von Herrath MG; Coon B; Oldstone MB. 1997. Low-affinity cytotoxic T-lymphocytes require IFN-gamma to clear an acute viral infection. Virology 229(2):349-59. [PubMed: 9126248] [MGI Ref ID J:127684]
von Herrath MG; Dockter J; Oldstone MB. 1994. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1(3):231-42. [PubMed: 7889411] [MGI Ref ID J:81287]
von Herrath MG; Oldstone MB. 1997. Interferon-gamma is essential for destruction of beta cells and development of insulin-dependent diabetes mellitus. J Exp Med 185(3):531-9. [PubMed: 9053453] [MGI Ref ID J:96856]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000651 BALB/cJ | (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. | ||
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
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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 and Purchasing Information
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