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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Background Strain C57BL/6 Donor Strain (C57BL/6 x BALB)F2 H2 Haplotype b Generation N16F?N17p (09-NOV-05) Donating Investigator Matthais von Herrath, La Jolla Institute for Allergy and Immun Appearance
black
Related Genotype: a/aDescription
Transgenic mice were created with the Lymphocytic choriomeningitis virus (LCMV) glycoprotein(GP) or nucleoprotein (NP) under the control of the rat insulin promoter. Ins2-GP expression was determined only in the pancreas by RT-PCR (von Herrath et al 1994). Tg(Ins2-GP)34-20Olds untreated mice rarely develop insulin-dependent diabetes mellitus (IDDM). When challenged with LCMV they develop IDDM. The B6.C -Tg(Ins2-GP)34-20Olds mice (H2b) exhibit a rapid (10-14 days) onset of IDDM compared to C.B6-Tg(Ins2-NP)25-3Olds mice (H2d) (10-21 days) or B6.C -Tg(Ins2-NP)25-3Olds mice (H2b) (30-120 days) (Oldstone et al.,1991; von Herrath et al.,1994). Thymic expression of nucleoprotein has been shown to be responsible for this delayed onset of IDDM. Thymi from newborn B6.C -Tg(Ins2-GP)34-20Olds transplanted into nude hosts produce a primary CTL response when challenged with LCMV. CD8 T cells are required for IDDM development in both glycoprotein and nucleoprotein transgenic mice, as is interferon gamma. In interferon gamma deficient transgenics stimulated 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)A singledose injection of anti CD80, anti CD86 or anti CD80/anti CD86 antibodies does not prevent LCMV induced diabetes in either the GP or NP 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
B6.C-Tg(Ins2-GP)34-20Olds/MvhJ expresses the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) 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 34-20, maintained by Herrath et al., (1994, 2000) has been backcrossed to C57BL/6 (H2b) for at least 10 generations. In 2005 this strain arrived at The Jackson Laboratory and is maintained Tg/? x Tg/?.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Ins2
View Strains carrying other alleles of Ins2 (45 strains)
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Ins2-GP)34-20Olds/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:81287)
- mice are considered diabetic after a blood glucose measure of >300 mg/dl
- immune system phenotype
- abnormal lymphocyte physiology (MGI Ref ID J:81287)
- on a B6 background, transgenic mice cannot exhibit a primary CTL response
- abnormal T cell physiology (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)
- mice rapidly develop diabetes (glucose levels >300 mg/dl) 10-14 days after viral (LCMV) challenge
- endocrine/exocrine gland phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:81287)
- mononuclear cells infiltrate the islets of transgenic mice 5-10 days after viral innoculation
- decreased pancreatic beta cell number (MGI Ref ID J:81287)
- no beta cells are detected at 14 days after LCMV infection
- digestive/alimentary phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:81287)
- mononuclear cells infiltrate the islets of transgenic mice 5-10 days after viral innoculation
- decreased pancreatic beta cell number (MGI Ref ID J:81287)
- no beta cells are detected at 14 days after LCMV infection
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
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Ins2-GP)34-20Olds | ||
|---|---|---|---|
| Allele Name | transgene insertion 34-20, Michael BA Oldstone, MD | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | LCMV GP; RIP GP H2; RIP GP34-20; RIP-GP34-20; RIP-LCMV GP; | ||
| Mutation Made By | Michael Oldstone, The Scripps Research Institute | ||
| Strain of Origin | (C57BL/6 x BALB/Wehi)F2 | ||
| Expressed Gene | GP, LCMV glycoprotein, | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | This transgene encodes the glycoprotein (GP) from Armstrong's clone of the lymphocytic choriomeningitis virus (LCMV) regulated by the rat insulin promoter. Upstream of the GP cDNA are 660 base pairs of regulatory elements in addition to the rat insulin promoter. Downstream of the GP c-DNA is the SV40 small T-antigen intron and late polyadenylation signal. RT-PCR analysis demonstrated that the transcript was expressed in the pancreas but not the thymus, spleen, liver, kidney, heart, muscle or lung. [MGI Ref ID J:81287] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Ins2-GP)34-20Olds, 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
Tg(Ins2-GP)34-20Olds relatedHall HT; Wilhelm MT; Saibil SD; Mak TW; Flavell RA; Ohashi PS. 2008. RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses. Eur J Immunol 38(1):64-72. [PubMed: 18085666] [MGI Ref ID J:130818]
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]
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]
Juedes AE; Rodrigo E; Togher L; Glimcher LH; von Herrath MG. 2004. T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes. J Exp Med 199(8):1153-62. [PubMed: 15096540] [MGI Ref ID J:121024]
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]
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; 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
Mating System +/+ sibling x Hemizygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| 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 Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| 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
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