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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names B6.Cg-Tg(Ins2-NP)25-3Scr/MvhJ (Changed: 31-MAR-05 ) 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 C57BL/6 Donor Strain (C57BL/6 x BALB)F2 H2 Haplotype b Generation N12+N4p (10-APR-05)
Generation DefinitionsDonating Investigator Dr. 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) 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.B6-Tg(Ins2-NP)25-3Olds (H2d) mice 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
B6.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 C57BL/6 (H2b) for at least 10 generations. In 2003 this strain arrived at The Jackson Laboratory and was backcrossed to C57BL/6J. This strain is maintained +/+ x hemizygote.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(Ins2-NP)25-3Olds allele
004827 C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ View Strains carrying Tg(Ins2-NP)25-3Olds (1 strain)
010632 NOD/ShiLt-Tg(INS-NP)6171Mvh/J
Phenotype
Phenotype Information
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Diabetes Mellitus, Insulin-Dependent; IDDM
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
- hypoinsulinemia is exhibited by transgenic mice accompanying increased glucose levels and islet infiltration (MGI Ref ID J:81287)
- increased circulating glucose level
- 3% of transgenic mice develop diabetes when followed for 10-12 months (MGI Ref ID J:81284)
- 93% of transgenic mice develop diabetes (hyperglycemia of >250 mg/dl glucose and islets infiltrated with mononuclear cells) after being infected with LCMV (MGI Ref ID J:81284)
- mice are considered diabetic after a blood glucose measure of >300 mg/dl (MGI Ref ID J:81287)
- endocrine/exocrine gland phenotype
- abnormal pancreatic islet morphology (MGI Ref ID J:81287)
- pancreata of diabetic transgenic mice show swollen islets with a ground glass appearance (MGI Ref ID J:81284)
- mononuclear cells begin infiltrating the islets 10 days after viral challenge and are apparent in most transgenic mice after 30 days (MGI Ref ID J:81284)
- 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 (MGI Ref ID J:81284)
- immune system phenotype
- decreased susceptibility to autoimmune diabetes
- depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes (MGI Ref ID J:81287)
- increased susceptibility to autoimmune diabetes
- 3% of transgenic mice develop diabetes when followed for 10-12 months (MGI Ref ID J:81287)
- 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 (MGI Ref ID J:81287)
- 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 (MGI Ref ID J:81287)
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Type 1 Diabetes
Research Tools
Diabetes and Obesity Research
Immunology and Inflammation Research
T Cell Receptor Transgenics
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Ins2-NP)25-3Olds | ||
|---|---|---|---|
| Allele Name | transgene insertion 25-3, Michael BA Oldstone, MD | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | RIP NP 25-3; RIP-LCMV; RIP-LCMV NP; | ||
| Mutation Made By | Dr. 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, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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 relatedBresson 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]
Christen S; Coppieters K; Rose K; Holdener M; Bayer M; Pfeilschifter JM; Hintermann E; von Herrath MG; Aurrand-Lions M; Imhof BA; Christen U. 2013. Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice. PLoS One 8(1):e54675. [PubMed: 23372751] [MGI Ref ID J:195794]
Diana J ; Griseri T ; Lagaye S ; Beaudoin L ; Autrusseau E ; Gautron AS ; Tomkiewicz C ; Herbelin A ; Barouki R ; von Herrath M ; Dalod M ; Lehuen A. 2009. NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner. Immunity 30(2):289-99. [PubMed: 19217323] [MGI Ref ID J:146623]
Filippi CM; Juedes AE; Oldham JE; Ling E; Togher L; Peng Y; Flavell RA; von Herrath MG. 2008. Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes 57(10):2684-92. [PubMed: 18689691] [MGI Ref ID J:142144]
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
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- 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
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- 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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- This strain is included in the Type 1 Diabetes Repository collection.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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 Information
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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