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Strain Name:

B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ

Stock Number:

004826

Availability:

Repository-Cryopreserved


General Terms and Conditions

Former Name      B6.Cg-Tg(Ins2-NP)25-3Scr/MvhJ    (Changed: 31-MAR-05 )
Genes & Alleles   Ins2;   NP;   Tg(Ins2-NP)25-3Olds;


Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain (C57BL/6 x BALB)F2
Donating Investigator Matthais von Herrath,   La Jolla Institute for Allergy and Immun
H2 Haplotypeb

Appearance
black
Related Genotype: a/a

Strain Description
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)

Strain 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.

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

Gene & Allele Details

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 OriginC57BL/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]

Control Information

  Control
   Noncarrier
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(Ins2-NP)25-3Olds

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

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)

Strains carrying other alleles of Ins2
005534   B10.Cg-H2d Tg(Ins2-HA)165Bri/ShrmJ
005500   B6.C-Tg(Ins2-GP)34-20Olds/MvhJ
005715   B6.Cg H2g7-Tg(Ins2-CD80)3B7Flv/LwnJ
003573   B6.Cg-Tg(Ins2-cre)25Mgn/J
005713   C.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
005533   C.Cg-Tg(Ins2-HA)165Bri/ShrmJ
005432   C57BL/6-Tg(Ins2-OVA)307Wehi/WehiJ
005433   C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ
005431   C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ
005564   FVB(Cg)-Tg(Ins2-CALM1)26Ove Tg(Cryaa-TAg)1Ove/PneJ
008232   FVB/N-Tg(Ins2-IAPP)RHFSoel/J
005522   NOD-Tg(Ins2*Y16A)1Ell/GseJ
005523   NOD-Tg(Ins2*Y16A)3Ell/GseJ
003499   NOD-Tg(Ins2-Fasl)24Ach
007840   NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ
004346   NOD.Cg-Prkdcscid Tg(Ins2-CD80)3B7Flv/DvsJ
004230   NOD.Cg-Prkdcscid Tg(Ins2-E3)1Dvs/DvsJ
003843   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ
003844   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ
005524   NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ
005525   NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ
006254   NOD.Cg-Tg(Ins2-Ccl21b)2Cys/JbsJ
006154   NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ
003869   NOD.Cg-Tg(Ins2-E3)1Dvs/DvsJ
005685   NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ
002380   NOD.Cg-Tg(Ins2-TAg)1Lt Prkdcscid/DvsJ
004602   NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
004937   NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ
005734   NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
005870   NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J
006777   NOD/ShiLt-Tg(Ins2-Cd274)2Mdos/MdosJ
005733   NOD/ShiLt-Tg(Ins2-Fas*I246N)1Ach/AchJ
003074   NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
004986   NOD/ShiLt-Tg(Ins2-cre)3Lt/Lt
003855   NOD/ShiLt-Tg(Ins2-cre)5Lt/LtJ
004987   NOD/ShiLt-Tg(Ins2-cre)6Lt/Lt
002033   NOD/ShiLt-Tg(RipTAg)1Lt/J
004990   NOD/ShiLtDvs-Tg(Ins2-E3*734)4Dvs/DvsJ
005714   NOR.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
008122   STOCK Tg(Ins2-cre/Esr1)1Dam/J
008250   STOCK Tg(Ins2-rtTA)2Efr/J
View Strains carrying other alleles of Ins2     (41 strains)

Additional Web Information

Congenic Nomenclature

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)

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

Price and Supply Information

Strain Name: B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ
Stock Number: 004826

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryopreserved Embryos
This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. 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 from our repository, please visit our Cryopreserved Embryos web page.
Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Type 1 Diabetes Repository collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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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.
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